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Accueil > Publications

Publications de l’I2BC

2018


  • N. Abdollahi, A. Albani, E. Anthony, A. Baud, M. Cardon, R. Clerc, D. Czernecki, R. Conte, L. David, A. Delaune, S. Djerroud, P. Fourgoux, N. Guiglielmoni, J. Laurentie, N. Lehmann, C. Lochard, R. Montagne, V. Myrodia, V. Opuu, E. Parey, L. Polit, S. Privé, C. Quignot, M. Ruiz-Cuevas, M. Sissoko, N. Sompairac, A. Vallerix, V. Verrecchia, M. Delarue, R. Guérois, Y. Ponty, S. Sacquin-Mora, A. Carbone, C. Froidevaux, S. Le Crom, O. Lespinet, M. Weigt, S. Abboud, J. Bernardes, G. Bouvier, C. Dequeker, A. Ferré, P. Fuchs, G. Lelandais, P. Poulain, H. Richard, H. Schweke, E. Laine, et A. Lopes, « Meet-U: Educating through research immersion », PLoS computational biology, vol. 14, nᵒ 3, p. e1005992, mars 2018.
    Résumé : We present a new educational initiative called Meet-U that aims to train students for collaborative work in computational biology and to bridge the gap between education and research. Meet-U mimics the setup of collaborative research projects and takes advantage of the most popular tools for collaborative work and of cloud computing. Students are grouped in teams of 4-5 people and have to realize a project from A to Z that answers a challenging question in biology. Meet-U promotes "coopetition," as the students collaborate within and across the teams and are also in competition with each other to develop the best final product. Meet-U fosters interactions between different actors of education and research through the organization of a meeting day, open to everyone, where the students present their work to a jury of researchers and jury members give research seminars. This very unique combination of education and research is strongly motivating for the students and provides a formidable opportunity for a scientific community to unite and increase its visibility. We report on our experience with Meet-U in two French universities with master's students in bioinformatics and modeling, with protein-protein docking as the subject of the course. Meet-U is easy to implement and can be straightforwardly transferred to other fields and/or universities. All the information and data are available at www.meet-u.org.
    Mots-clés : AMIG, B3S, BDG, BIM.

  • A. Abou-Hamdan, L. Belot, A. Albertini, et Y. Gaudin, « Monomeric Intermediates Formed by Vesiculovirus Glycoprotein during Its Low-pH-induced Structural Transition », Journal of Molecular Biology, avr. 2018.
    Mots-clés : conformational change, glycoprotein, Influenza, membrane fusion, RHABDO, Vesiculovirus, VIRO.


  • C. Adam, R. Guérois, A. Citarella, L. Verardi, F. Adolphe, C. Béneut, V. Sommermeyer, C. Ramus, J. Govin, Y. Couté, et V. Borde, « The PHD finger protein Spp1 has distinct functions in the Set1 and the meiotic DSB formation complexes », PLOS Genetics, vol. 14, nᵒ 2, p. e1007223, févr. 2018.

  • N. Agier, S. Delmas, Q. Zhang, A. Fleiss, Y. Jaszczyszyn, E. van Dijk, C. Thermes, M. Weigt, M. Cosentino-Lagomarsino, et G. Fischer, « The evolution of the temporal program of genome replication », Nature Communications, vol. 9, nᵒ 1, p. 2199, juin 2018.
    Résumé : Genome replication is highly regulated in time and space, but the rules governing the remodeling of these programs during evolution remain largely unknown. We generated genome-wide replication timing profiles for ten Lachancea yeasts, covering a continuous evolutionary range from closely related to more divergent species. We show that replication programs primarily evolve through a highly dynamic evolutionary renewal of the cohort of active replication origins. We found that gained origins appear with low activity yet become more efficient and fire earlier as they evolutionarily age. By contrast, origins that are lost comprise the complete range of firing strength. Additionally, they preferentially occur in close vicinity to strong origins. Interestingly, despite high evolutionary turnover, active replication origins remain regularly spaced along chromosomes in all species, suggesting that origin distribution is optimized to limit large inter-origin intervals. We propose a model on the evolutionary birth, death, and conservation of active replication origins.
    Mots-clés : CHERDIR, NGS, PF.

  • L. Ahmad, S. Plancqueel, V. Dubosclard, N. Lazar, W. Ghattas, I. Li de la Sierra-Gallay, H. van Tilbeurgh, et L. Salmon, « Crystal structure of phosphomannose isomerase from Candida albicans complexed with 5-phospho-d-arabinonhydrazide », FEBS letters, vol. 592, nᵒ 10, p. 1667-1680, mai 2018.
    Résumé : Type I phosphomannose isomerases (PMIs) are zinc-dependent monofunctional metalloenzymes catalysing the reversible isomerization of d-mannose 6-phosphate to d-fructose 6-phosphate. 5-Phospho-d-arabinonhydrazide (5PAHz), designed as an analogue of the enediolate high-energy intermediate, strongly inhibits PMI from Candida albicans (CaPMI). In this study, we report the 3D crystal structure of CaPMI complexed with 5PAHz at 1.85 Å resolution. The high-resolution structure suggests that Glu294 is the catalytic base that transfers a proton between the C1 and C2 carbon atoms of the substrate. Bidentate coordination of the inhibitor explains the stereochemistry of the isomerase activity, as well as the absence of both anomerase and C2-epimerase activities for Type I PMIs. A detailed mechanism of the reversible isomerization is proposed.
    Mots-clés : B3S, Candida albicans, enzyme mechanism, FAAM, inhibitor, phosphomannose isomerase, zinc metalloenzyme.

  • G. Annio, T. L. Jennings, O. Tagit, et N. Hildebrandt, « Sensitivity Enhancement of Förster Resonance Energy Transfer Immunoassays by Multiple Antibody Conjugation on Quantum Dots », Bioconjugate Chemistry, vol. 29, nᵒ 6, p. 2082-2089, juin 2018.
    Résumé : Quantum dots (QDs) are not only advantageous for color-tuning, improved brightness, and high stability, but their nanoparticle surfaces also allow for the attachment of many biomolecules. Because IgG antibodies (AB) are in the same size range of biocompatible QDs and the AB orientation after conjugation to the QD is often random, it is difficult to predict if few or many AB per QD will lead to an efficient AB-QD conjugate. This is particularly true for homogeneous Förster resonance energy transfer (FRET) sandwich immunoassays, for which the AB on the QD must bind a biomarker that needs to bind a second AB-FRET-conjugate. Here, we investigate the performance of Tb-to-QD FRET immunoassays against total prostate specific antigen (TPSA) by changing the number of AB per QD while leaving all the other assay components unchanged. We first characterize the AB-QD conjugation by various spectroscopic, microscopic, and chromatographic techniques and then quantify the TPSA immunoassay performance regarding sensitivity, limit of detection, and dynamic range. Our results show that an increasing conjugation ratio leads to significantly enhanced FRET immunoassays. These findings will be highly important for developing QD-based immunoassays in which the concentrations of both AB and QDs can significantly influence the assay performance.
    Mots-clés : B3S, NANO.

  • M. Ansaldi, L. Debarbieux, S. Gandon, M. - A. Petit, P. Tavares, et P. Boulanger, « "French Phage Network"-Third Meeting Report », Viruses, vol. 10, nᵒ 3, mars 2018.
    Résumé : In its third year of existence, the French Phage Network (Phages.fr) is pursuing its expansion. With more than 25 groups, mostly based in France, working on the various aspects of phage research, the network has increased its visibility, interactivity, and activity. The third meeting of the Phages.fr network, held on November 2017 at the Gif-sur-Yvette Centre National de la Recherche Scientifique (CNRS) campus, was a great opportunity for many young scientists to present their work and interact with more senior scientists, amongst which several were invited from abroad. Here we provide a summary of the work presented at this occasion during the oral presentations and poster sessions.
    Mots-clés : bacteria, bacteriophage, co-evolution, France, genomics, infection, PHAG+, phage therapy, resistance, structural biology, T5PHAG, VIRO, virulence.

  • J. - M. Arbona, A. Goldar, O. Hyrien, A. Arneodo, et B. Audit, « The eukaryotic bell-shaped temporal rate of DNA replication origin firing emanates from a balance between origin activation and passivation », eLife, vol. 7, juin 2018.
    Résumé : The time-dependent rate I(t) of origin firing per length of unreplicated DNA presents a universal bell shape in eukaryotes that has been interpreted as the result of a complex time-evolving interaction between origins and limiting firing factors. Here we show that a normal diffusion of replication fork components towards localized potential replication origins (p-oris) can more simply account for the I(t) universal bell shape, as a consequence of a competition between the origin firing time and the time needed to replicate DNA separating two neighboring p-oris. We predict the I(t) maximal value to be the product of the replication fork speed with the squared p-ori density. We show that this relation is robustly observed in simulations and in experimental data for several eukaryotes. Our work underlines that fork-component recycling and potential origins localization are sufficient spatial ingredients to explain the universality of DNA replication kinetics.
    Mots-clés : BDG, chromosomes, computational biology, gene expression, GTR, human, S. cerevisiae, systems biology.


  • T. Avin-Wittenberg, F. Baluška, P. V. Bozhkov, P. H. Elander, A. R. Fernie, G. Galili, A. Hassan, D. Hofius, E. Isono, R. Le Bars, C. Masclaux-Daubresse, E. A. Minina, H. Peled-Zehavi, N. S. Coll, L. M. Sandalio, B. Satiat-Jeunemaitre, A. Sirko, P. S. Testillano, et H. Batoko, « Autophagy-related approaches for improving nutrient use efficiency and crop yield protection », Journal of Experimental Botany, vol. 69, nᵒ 6, p. 1335-1353, mars 2018.
    Mots-clés : BIOCELL, CYTO, DYNBSJ, PF, PHOT.

  • T. Avin-Wittenberg, F. Baluška, P. V. Bozhkov, P. H. Elander, A. R. Fernie, G. Galili, A. Hassan, D. Hofius, E. Isono, R. Le Bars, C. Masclaux-Daubresse, E. A. Minina, H. Peled-Zehavi, N. S. Coll, L. M. Sandalio, B. Satiat-Jeunemaitre, A. Sirko, P. S. Testillano, et H. Batoko, « Corrigendum: Autophagy-related approaches for improving nutrient use efficiency and crop yield protection », Journal of Experimental Botany, vol. 69, nᵒ 12, p. 3173, mai 2018.
    Mots-clés : BIOCELL, CYTO, DYNBSJ, PF, PHOT.

  • A. Barwinska-Sendra, A. Baslé, K. J. Waldron, et S. Un, « A charge polarization model for the metal-specific activity of superoxide dismutases », Physical chemistry chemical physics: PCCP, janv. 2018.
    Résumé : The pathogenicity of Staphylococcus aureus is enhanced by having two superoxide dismutases (SODs): a Mn-specific SOD and another that can use either Mn or Fe. Using 94 GHz electron-nuclear double resonance (ENDOR) and electron double resonance detected (ELDOR)-NMR we show that, despite their different metal-specificities, their structural and electronic similarities extend down to their active-site 1H- and 14N-Mn(ii) hyperfine interactions. However these interactions, and hence the positions of these nuclei, are different in the inactive Mn-reconstituted Escherichia coli Fe-specific SOD. Density functional theory modelling attributes this to a different angular position of the E. coli H171 ligand. This likely disrupts the Mn-H171-E170' triad causing a shift in charge and in metal redox potential, leading to the loss of activity. This is supported by the correlated differences in the Mn(ii) zero-field interactions of the three SOD types and suggests that the triad is important for determining metal specific activity.
    Mots-clés : B3S, BHFMR.

  • E. L. Bastow, V. S. Garcia de la Torre, A. E. Maclean, R. T. Green, S. Merlot, S. Thomine, et J. Balk, « Vacuolar iron stores gated by NRAMP3 and NRAMP4 are the primary source of iron in germinating seeds », Plant Physiology, vol. 177, nᵒ 3, p. 1267-1276, mai 2018.
    Résumé : During seed germination, iron (Fe) stored in vacuoles is exported by the redundant NRAMP3 and NRAMP4 transporter proteins. A double nramp3 nramp4 mutant is unable to mobilize Fe stores and does not develop in the absence of external Fe. We used RNA sequencing to compare gene expression in nramp3 nramp4 and wild type during germination and early seedling development. Even though sufficient Fe was supplied, the Fe-responsive transcription factors bHLH38, 39, 100 and 101 and their downstream targets FRO2 and IRT1 mediating Fe uptake were strongly upregulated in the nramp3 nramp4 mutant. Activation of the Fe deficiency response was confirmed by increased ferric chelate reductase activity in the mutant. At early stages, genes important for chloroplast redox control (FSD1, SAPX), Fe homeostasis (FER1, SUFB) and chlorophyll metabolism (HEMA1, NYC1) were downregulated, indicating limited Fe availability in plastids. In contrast, expression of FRO3, encoding a ferric reductase involved in Fe import into the mitochondria, was maintained and Fe-dependent enzymes in the mitochondria were unaffected in nramp3 nramp4. Together these data show that a failure to mobilize Fe stores during germination triggered Fe deficiency responses and strongly affected plastids but not mitochondria.
    Mots-clés : BIOCELL, MINION.

  • A. Belyy, U. Mechold, L. Renault, et D. Ladant, « ExoY, an actin-activated nucleotidyl cyclase toxin from P. aeruginosa: A minireview », Toxicon: Official Journal of the International Society on Toxinology, vol. 149, p. 65-71, juill. 2018.
    Résumé : ExoY is one of four well-characterized Pseudomonas aeruginosa type 3 secretion system (T3SS) effectors. It is a nucleotidyl cyclase toxin that is inactive inside the bacteria, but becomes potently activated once it is delivered into the eukaryotic target cells. Recently, filamentous actin was identified as the eukaryotic cofactor that stimulates specifically ExoY enzymatic activity by several orders of magnitude. In this review, we discuss recent advances in understanding the biochemistry of nucleotidyl cyclase activity of ExoY and its regulation by interaction with filamentous actin.
    Mots-clés : ACTIN.

  • A. Berto, J. Yu, S. Morchoisne-Bolhy, C. Bertipaglia, R. Vallee, J. Dumont, F. Ochsenbein, R. Guerois, et V. Doye, « Disentangling the molecular determinants for Cenp-F localization to nuclear pores and kinetochores », EMBO reports, vol. 19, nᵒ 5, mai 2018.
    Résumé : Cenp-F is a multifaceted protein implicated in cancer and developmental pathologies. The Cenp-F C-terminal region contains overlapping binding sites for numerous proteins that contribute to its functions throughout the cell cycle. Here, we focus on the nuclear pore protein Nup133 that interacts with Cenp-F both at nuclear pores in prophase and at kinetochores in mitosis, and on the kinase Bub1, known to contribute to Cenp-F targeting to kinetochores. By combining in silico structural modeling and yeast two-hybrid assays, we generate an interaction model between a conserved helix within the Nup133 β-propeller and a short leucine zipper-containing dimeric segment of Cenp-F. We thereby create mutants affecting the Nup133/Cenp-F interface and show that they prevent Cenp-F localization to the nuclear envelope, but not to kinetochores. Conversely, a point mutation within an adjacent leucine zipper affecting the kinetochore targeting of Cenp-F KT-core domain impairs its interaction with Bub1, but not with Nup133, identifying Bub1 as the direct KT-core binding partner of Cenp-F. Finally, we show that Cenp-E redundantly contributes together with Bub1 to the recruitment of Cenp-F to kinetochores.
    Mots-clés : AMIG, B3S, Cenp‐F, in silico modeling, kinetochores, mitosin, nuclear pore.


  • S. Blanchet, D. Cornu, I. Hatin, H. Grosjean, P. Bertin, et O. Namy, « Deciphering the reading of the genetic code by near-cognate tRNA », Proceedings of the National Academy of Sciences, vol. 115, nᵒ 12, p. 3018-3023, mars 2018.

  • S. Bouffard, E. Dambroise, A. Brombin, S. Lempereur, I. Hatin, M. Simion, R. Corre, F. Bourrat, J. - S. Joly, et F. Jamen, « Fibrillarin is essential for S-phase progression and neuronal differentiation in zebrafish dorsal midbrain and retina », Developmental Biology, févr. 2018.
    Résumé : Fibrillarin (Fbl) is a highly conserved protein that plays an essential role in ribosome biogenesis and more particularly in the methylation of ribosomal RNAs and rDNA histones. In cellular models, FBL was shown to play an important role in tumorigenesis and stem cell differentiation. We used the zebrafish as an in vivo model to study Fbl function during embryonic development. We show here that the optic tectum and the eye are severely affected by Fbl depletion whereas ventral regions of the brain are less impacted. The morphogenesis defects are associated with impaired neural differentiation and massive apoptosis. Polysome gradient experiments show that fbl mutant larvae display defects in ribosome biogenesis and activity. Strikingly, flow cytometry analyses revealed different S-phase profiles between wild-type and mutant cells, suggesting a defect in S-phase progression.
    Mots-clés : BDG, Cell cycle regulation, Danio rerio, Differentiation, GST, Neural progenitors, Optic tectum, Ribosome biogenesis.


  • G. Bourgeois, J. Seguin, M. Babin, P. Belin, M. Moutiez, Y. Mechulam, M. Gondry, et E. Schmitt, « Structural basis for partition of the cyclodipeptide synthases into two subfamilies », Journal of Structural Biology, vol. 203, nᵒ 1, p. 17-26, juill. 2018.
    Résumé : Cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines. It was shown that CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. However, current understanding of CDPSs only comes from studies of enzymes from the NYH subfamily. The present study reveals the crystal structures of three CDPSs from the XYP subfamily. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. This gives a structural basis for the partition of CDPSs into two subfamilies. Despite these differences, the catalytic residues adopt similar positioning regardless of the subfamily suggesting that the XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue.
    Mots-clés : Aminoacyl-tRNA synthetases, BIOSYN, Cyclodipeptides, Diketopiperazines, MICROBIO, Non-ribosomal peptide synthesis, Rossmann fold, Transfer RNA.

  • A. Boussac, I. Ugur, A. Marion, M. Sugiura, V. R. I. Kaila, et A. W. Rutherford, « The low spin - high spin equilibrium in the S2-state of the water oxidizing enzyme », Biochimica Et Biophysica Acta, vol. 1859, nᵒ 5, p. 342-356, févr. 2018.
    Résumé : In Photosystem II (PSII), the Mn4CaO5-cluster of the active site advances through five sequential oxidation states (S0to S4) before water is oxidized and O2is generated. Here, we have studied the transition between the low spin (LS) and high spin (HS) configurations of S2using EPR spectroscopy, quantum chemical calculations using Density Functional Theory (DFT), and time-resolved UV-visible absorption spectroscopy. The EPR experiments show that the equilibrium between S2LSand S2HSis pH dependent, with a pKa ≈ 8.3 (n ≈ 4) for the native Mn4CaO5and pKa ≈ 7.5 (n ≈ 1) for Mn4SrO5. The DFT results suggest that exchanging Ca with Sr modifies the electronic structure of several titratable groups within the active site, including groups that are not direct ligands to Ca/Sr, e.g., W1/W2, Asp61, His332 and His337. This is consistent with the complex modification of the pKaupon the Ca/Sr exchange. EPR also showed that NH3addition reversed the effect of high pH, NH3-S2LSbeing present at all pH values studied. Absorption spectroscopy indicates that NH3is no longer bound in the S3TyrZstate, consistent with EPR data showing minor or no NH3-induced modification of S3and S0. In both Ca-PSII and Sr-PSII, S2HSwas capable of advancing to S3at low temperature (198 K). This is an experimental demonstration that the S2LSis formed first and advances to S3via the S2HSstate without detectable intermediates. We discuss the nature of the changes occurring in the S2LSto S2HStransition which allow the S2HSto S3transition to occur below 200 K. This work also provides a protocol for generating S3in concentrated samples without the need for saturating flashes.
    Mots-clés : B3S, DFT, EPR, Mn(4)CaO(5) cluster, Oxygen evolution, Photosystem II, PS2, Spin state.

  • M. Byrdin, C. Duan, D. Bourgeois, et K. Brettel, « A Long-Lived Triplet State Is the Entrance Gateway to Oxidative Photochemistry in Green Fluorescent Proteins », Journal of the American Chemical Society, vol. 140, nᵒ 8, p. 2897-2905, févr. 2018.
    Résumé : Though ubiquitously used as selective fluorescence markers in cellular biology, fluorescent proteins (FPs) still have not disclosed all of their surprising properties. One important issue, notably for single-molecule applications, is the nature of the triplet state, suggested to be the starting point for many possible photochemical reactions leading to phenomena such as blinking or bleaching. Here, we applied transient absorption spectroscopy to characterize dark states in the prototypical enhanced green fluorescent protein (EGFP) of hydrozoan origin and, for comparison, in IrisFP, a representative phototransformable FP of anthozoan origin. We identified a long-lived (approximately 5 ms) dark state that is formed with a quantum yield of approximately 1% and has pronounced absorption throughout the visible-NIR range (peak at around 900 nm). Detection of phosphorescence emission with identical kinetics and excitation spectrum allowed unambiguous identification of this state as the first excited triplet state of the deprotonated chromophore. This triplet state was further characterized by determining its phosphorescence emission spectrum, the temperature dependence of its decay kinetics and its reactivity toward oxygen and electron acceptors and donors. It is suggested that it is this triplet state that lies at the origin of oxidative photochemistry in green FPs, leading to phenomena such as so-called "oxidative redding", "primed photoconversion", or, in a manner similar to that previously observed for organic dyes, redox induced blinking control with the reducing and oxidizing system ("ROXS").
    Mots-clés : B3S, LPB.

  • T. Candelli, D. Challal, J. - B. Briand, J. Boulay, O. Porrua, J. Colin, et D. Libri, « High-resolution transcription maps reveal the widespread impact of roadblock termination in yeast », The EMBO journal, janv. 2018.
    Résumé : Transcription termination delimits transcription units but also plays important roles in limiting pervasive transcription. We have previously shown that transcription termination occurs when elongating RNA polymerase II (RNAPII) collides with the DNA-bound general transcription factor Reb1. We demonstrate here that many different DNA-binding proteins can induce termination by a similar roadblock (RB) mechanism. We generated high-resolution transcription maps by the direct detection of RNAPII upon nuclear depletion of two essential RB factors or when the canonical termination pathways for coding and non-coding RNAs are defective. We show that RB termination occurs genomewide and functions independently of (and redundantly with) the main transcription termination pathways. We provide evidence that transcriptional readthrough at canonical terminators is a significant source of pervasive transcription, which is controlled to a large extent by RB termination. Finally, we demonstrate the occurrence of RB termination around centromeres and tRNA genes, which we suggest shields these regions from RNAPII to preserve their functional integrity.
    Mots-clés : BDG, DBG, pervasive transcription, Rap1, roadblock termination, TENOR, transcription readthrough, transcription termination mechanism.

  • N. Canu, P. Belin, R. Thai, I. Correia, O. Lequin, J. Seguin, M. Moutiez, et M. Gondry, « Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases », Angewandte Chemie (International Ed. in English), vol. 57, nᵒ 12, p. 3118-3122, mars 2018.
    Résumé : The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates. We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5-DKPs. Such diversity could be further expanded, for example, by using various cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways.
    Mots-clés : biocatalysis, BIOSYN, biosynthesis, Cyclodipeptide synthases, cyclodipeptides, Diketopiperazines, MICROBIO, Natural product engineering, Non-canonical amino acid.


  • M. Cardoso Dos Santos, J. Goetz, H. Bartenlian, K. - L. Wong, L. J. Charbonnière, et N. Hildebrandt, « Autofluorescence-Free Live-Cell Imaging Using Terbium Nanoparticles », Bioconjugate Chemistry, févr. 2018.


  • D. Carmona-Gutierrez, M. A. Bauer, A. Zimmermann, A. Aguilera, N. Austriaco, K. Ayscough, R. Balzan, S. Bar-Nun, A. Barrientos, P. Belenky, M. Blondel, R. J. Braun, M. Breitenbach, W. C. Burhans, S. Buettner, D. Cavalieri, M. Chang, K. F. Cooper, M. Côrte-Real, V. Costa, C. Cullin, I. Dawes, J. Dengjel, M. B. Dickman, T. Eisenberg, B. Fahrenkrog, N. Fasel, K. - U. Froehlich, A. Gargouri, S. Giannattasio, P. Goffrini, C. W. Gourlay, C. M. Grant, M. T. Greenwood, N. Guaragnella, T. Heger, J. Heinisch, E. Herker, J. M. Herrmann, S. Hofer, A. Jiménez-Ruiz, H. Jungwirth, K. Kainz, D. P. Kontoyiannis, P. Ludovico, S. Manon, E. Martegani, C. Mazzoni, L. A. Megeney, C. Meisinger, J. Nielsen, T. Nystroem, H. D. Osiewacz, T. F. Outeiro, H. - O. Park, T. Pendl, D. Petranovic, S. Picot, P. Polčic, T. Powers, M. Ramsdale, M. Rinnerthaler, P. Rockenfeller, C. Ruckenstuhl, R. Schaffrath, M. Segovia, F. F. Severin, A. Sharon, S. J. Sigrist, C. Sommer-Ruck, M. J. Sousa, J. M. Thevelein, K. Thevissen, V. Titorenko, M. B. Toledano, M. Tuite, F. - N. Voegtle, B. Westermann, J. Winderickx, S. Wissing, S. Woelfl, Z. J. Zhang, R. Y. Zhao, B. Zhou, L. Galluzzi, G. Kroemer, et F. Madeo, « Guidelines and recommendations on yeast cell death nomenclature », Microbial Cell, vol. 5, nᵒ 1, p. 4-31, janv. 2018.

  • B. Castrec, C. Dian, S. Ciccone, C. L. Ebert, W. V. Bienvenut, J. - P. Le Caer, J. - M. Steyaert, C. Giglione, et T. Meinnel, « Structural and genomic decoding of human and plant myristoylomes reveals a definitive recognition pattern », Nature Chemical Biology, juin 2018.
    Résumé : An organism's entire protein modification repertoire has yet to be comprehensively mapped. N-myristoylation (MYR) is a crucial eukaryotic N-terminal protein modification. Here we mapped complete Homo sapiens and Arabidopsis thaliana myristoylomes. The crystal structures of human modifier NMT1 complexed with reactive and nonreactive target-mimicking peptide ligands revealed unexpected binding clefts and a modifier recognition pattern. This information allowed integrated mapping of myristoylomes using peptide macroarrays, dedicated prediction algorithms, and in vivo mass spectrometry. Global MYR profiling at the genomic scale identified over a thousand novel, heterogeneous targets in both organisms. Surprisingly, MYR involved a non-negligible set of overlapping targets with N-acetylation, and the sequence signature marks for a third proximal acylation-S-palmitoylation-were genomically imprinted, allowing recognition of sequences exhibiting both acylations. Together, the data extend the N-end rule concept for Gly-starting proteins to subcellular compartmentalization and reveal the main neighbors influencing protein modification profiles and consequent cell fate.
    Mots-clés : BDG, PROMTI.

  • R. Catchpole, A. Gorlas, J. Oberto, et P. Forterre, « A series of new E. coli-Thermococcus shuttle vectors compatible with previously existing vectors », Extremophiles: Life Under Extreme Conditions, vol. 22, nᵒ 4, p. 591-598, juill. 2018.
    Résumé : Hyperthermophilic microorganisms are an important asset in the toolkits of biotechnologists, biochemists and evolutionary biologists. The anaerobic archaeon, Thermococcus kodakarensis, has become one of the most useful hyperthermophilic model species, not least due to its natural competence and genetic tractability. Despite this, the range of genetic tools available for T. kodakarensis remains limited. Using sequencing and phylogenetic analyses, we determined that the rolling-circle replication origin of the cryptic mini-plasmid pTP2 from T. prieurii is suitable for plasmid replication in T. kodakarensis. Based on this replication origin, we present a novel series of replicative E. coli-T. kodakarensis shuttle vectors. These shuttle vectors have been constructed with three different selectable markers, allowing selection in a range of T. kodakarensis backgrounds. Moreover, these pTP2-derived plasmids are compatible with the single-existing E. coli-T. kodakarensis shuttle vector, pLC70. We show that both pTP2-derived and pLC70-derived plasmids replicate faithfully while cohabitating in T. kodakarensis cells. These plasmids open the door for new areas of research in plasmid segregation, DNA replication and gene expression.
    Mots-clés : Archaea, ARCHEE, Cloning, Gene cloning and expression, Genetics of extremophiles, Hyperthermophiles, MICROBIO, Molecular biology, Molecular biology of archaea.

  • F. Celli, A. Petitalot, C. Samson, F. - X. Theillet, et S. Zinn-Justin, « 1 H,13C and15N backbone resonance assignment of the lamin C-terminal region specific to prelamin A », Biomolecular NMR assignments, mars 2018.
    Résumé : Lamins are the main components of the nucleoskeleton. They form a protein meshwork that underlies the inner nuclear membrane. Mutations in the LMNA gene coding for A-type lamins (lamins A and C) cause a large panel of human diseases, referred to as laminopathies. These diseases include muscular dystrophies, lipodystrophies and premature aging diseases. Lamin A exhibits a C-terminal region that is different from lamin C and is post-translationally modified. It is produced as prelamin A and it is then farnesylated, cleaved, carboxymethylated and cleaved again in order to become mature lamin A. In patients with the severe Hutchinson-Gilford progeria syndrome, a specific single point mutation in LMNA leads to an aberrant splicing of the LMNA gene preventing the post-translational processing of prelamin A. This leads to the accumulation of a permanently farnesylated lamin A mutant lacking 50 amino acids named progerin. We here report the NMR1H,15N,13CO,13Cα and13Cβ chemical shift assignment of the C-terminal region that is specific to prelamin A, from amino acid 567 to amino acid 664. We also report the NMR1H,15N,13CO,13Cα and13Cβ chemical shift assignment of the C-terminal region of the progerin variant, from amino acid 567 to amino acid 614. Analysis of these chemical shift data confirms that both prelamin A and progerin C-terminal domains are largely disordered and identifies a common partially populated α-helix from amino acid 576 to amino acid 585. This helix is well conserved from fishes to mammals.
    Mots-clés : B3S, INTGEN, Intrinsically disordered protein, NMR spectroscopy, Nuclear envelope, Nucleoskeleton.


  • C. Chaintreuil, X. Perrier, G. Martin, J. Fardoux, G. P. Lewis, L. Brottier, R. Rivallan, M. Gomez-Pacheco, M. Bourges, L. Lamy, B. Thibaud, H. Ramanankierana, H. Randriambanona, H. Vandrot, P. Mournet, E. Giraud, et J. - F. Arrighi, « Naturally occurring variations in the nod-independent model legume Aeschynomene evenia and relatives: a resource for nodulation genetics », BMC Plant Biology, vol. 18, nᵒ 1, 2018.

  • H. - J. Chang, P. Mayonove, A. Zavala, A. De Visch, P. Minard, M. Cohen-Gonsaud, et J. Bonnet, « A Modular Receptor Platform To Expand the Sensing Repertoire of Bacteria », ACS synthetic biology, vol. 7, nᵒ 1, p. 166-175, janv. 2018.
    Résumé : Engineered bacteria promise to revolutionize diagnostics and therapeutics, yet many applications are precluded by the limited number of detectable signals. Here we present a general framework to engineer synthetic receptors enabling bacterial cells to respond to novel ligands. These receptors are activated via ligand-induced dimerization of a single-domain antibody fused to monomeric DNA-binding domains (split-DBDs). Using E. coli as a model system, we engineer both transmembrane and cytosolic receptors using a VHH for ligand detection and demonstrate the scalability of our platform by using the DBDs of two different transcriptional regulators. We provide a method to optimize receptor behavior by finely tuning protein expression levels and optimizing interdomain linker regions. Finally, we show that these receptors can be connected to downstream synthetic gene circuits for further signal processing. The general nature of the split-DBD principle and the versatility of antibody-based detection should support the deployment of these receptors into various hosts to detect ligands for which no receptor is found in nature.
    Mots-clés : B3S, MIP.

  • G. Chararalambidis, S. Das, A. Trapali, A. Quaranta, M. Orio, Z. Halime, P. Fertey, R. Guillot, A. Coutsolelos, W. Leibl, A. Aukauloo, et M. Sircoglou, « Water Molecules Gating a Photoinduced One Electron Two Protons Transfer in a Tyr/His model of Photosystem II », Angewandte Chemie (International Ed. in English), mai 2018.
    Résumé : In this report, we investigate on a biomimetic model of a H-bonded TyrZ/His190 pair covalently attached to a porphyrin sensitizer. Laser flash photolysis in presence of an external electron acceptor reveals the need of water molecules to unlock the light-induced oxidation of the phenol through an intramolecular pathway. Kinetics monitoring encompasses two fast phases with distinct spectral properties. The first phase is related to one-electron transfer from the phenol to the porphyrin radical cation coupled with a domino two-proton transfer leading to the ejection of a proton from the imidazole-phenol pair. The second phase concerns the convoy of the released proton to the porphyrin N4 coordinating cavity. Importantly, our study provides an unprecedented example of light induced electron transfer process in a TyrZ/His190 model of Photosystem II, evidencing the movement of both the phenol and imidazole protons along an isoenergetic pathway.
    Mots-clés : artificial photosynthesis, B3S, LPB, Proton Coupled Electron Transfer, TyrZ-His190 model.

  • M. Chaumorcel, M. Lussignol, L. Mouna, Y. Cavignac, K. Fahie, J. Cotte-Laffitte, A. Geballe, W. Brune, I. Beau, P. Codogno, et A. Esclatine, « Correction for Chaumorcel et al., "The Human Cytomegalovirus Protein TRS1 Inhibits Autophagy via Its Interaction with Beclin 1" », Journal of Virology, vol. 92, nᵒ 9, 2018.

  • J. - H. Chen, L. - J. Yu, A. Boussac, Z. - Y. Wang-Otomo, T. Kuang, et J. - R. Shen, « Properties and structure of a low-potential, penta-heme cytochrome c 552 from a thermophilic purple sulfur photosynthetic bacterium Thermochromatium tepidum », Photosynthesis Research, avr. 2018.
    Résumé : The thermophilic purple sulfur bacterium Thermochromatium tepidum possesses four main water-soluble redox proteins involved in the electron transfer behavior. Crystal structures have been reported for three of them: a high potential iron-sulfur protein, cytochrome c', and one of two low-potential cytochrome c 552 (which is a flavocytochrome c) have been determined. In this study, we purified another low-potential cytochrome c 552 (LPC), determined its N-terminal amino acid sequence and the whole gene sequence, characterized it with absorption and electron paramagnetic spectroscopy, and solved its high-resolution crystal structure. This novel cytochrome was found to contain five c-type hemes. The overall fold of LPC consists of two distinct domains, one is the five heme-containing domain and the other one is an Ig-like domain. This provides a representative example for the structures of multiheme cytochromes containing an odd number of hemes, although the structures of multiheme cytochromes with an even number of hemes are frequently seen in the PDB database. Comparison of the sequence and structure of LPC with other proteins in the databases revealed several characteristic features which may be important for its functioning. Based on the results obtained, we discuss the possible intracellular function of this LPC in Tch. tepidum.
    Mots-clés : B3S, Crystal structure, Cytochrome c, Electron transfer, Multiheme, PS2, Purple sulfur bacteria, Thermochromatium tepidum.
  • M. Chevreuil, D. Law-Hine, J. Chen, S. Bressanelli, S. Combet, D. Constantin, J. Degrouard, J. Möller, M. Zeghal, et G. Tresset, « Nonequilibrium self-assembly dynamics of icosahedral viral capsids packaging genome or polyelectrolyte », 2018.
    Mots-clés : disassembly, kinetic pathway, Modeling, time-resolved small-angle X-ray scattering, Virus.

  • R. R. Choubeh, E. Wientjes, P. C. Struik, D. Kirilovsky, et H. van Amerongen, « State transitions in the cyanobacterium Synechococcus elongatus 7942 involve reversible quenching of the photosystem II core », Biochimica Et Biophysica Acta, juin 2018.
    Résumé : Cyanobacteria use chlorophyll and phycobiliproteins to harvest light. The resulting excitation energy is delivered to reaction centers (RCs), where photochemistry starts. The relative amounts of excitation energy arriving at the RCs of photosystem I (PSI) and II (PSII) depend on the spectral composition of the light. To balance the excitations in both photosystems, cyanobacteria perform state transitions to equilibrate the excitation energy. They go to state I if PSI is preferentially excited, for example after illumination with blue light (light I), and to state II after illumination with green-orange light (light II) or after dark adaptation. In this study, we performed 77-K time-resolved fluorescence spectroscopy on wild-type Synechococcus elongatus 7942 cells to measure how state transitions affect excitation energy transfer to PSI and PSII in different light conditions and to test the various models that have been proposed in literature. The time-resolved spectra show that the PSII core is quenched in state II and that this is not due to a change in excitation energy transfer from PSII to PSI (spill-over), either direct or indirect via phycobilisomes.
    Mots-clés : B3S, Cyanobacteria, MROP, Photosystem II, State transitions, Time-resolved fluorescence spectroscopy.


  • F. Coll, J. Phelan, G. A. Hill-Cawthorne, M. B. Nair, K. Mallard, S. Ali, A. M. Abdallah, S. Alghamdi, M. Alsomali, A. O. Ahmed, S. Portelli, Y. Oppong, A. Alves, T. B. Bessa, S. Campino, M. Caws, A. Chatterjee, A. C. Crampin, K. Dheda, N. Furnham, J. R. Glynn, L. Grandjean, D. Minh Ha, R. Hasan, Z. Hasan, M. L. Hibberd, M. Joloba, E. C. Jones-López, T. Matsumoto, A. Miranda, D. J. Moore, N. Mocillo, S. Panaiotov, J. Parkhill, C. Penha, J. Perdigão, I. Portugal, Z. Rchiad, J. Robledo, P. Sheen, N. T. Shesha, F. A. Sirgel, C. Sola, E. Oliveira Sousa, E. M. Streicher, P. V. Helden, M. Viveiros, R. M. Warren, R. McNerney, A. Pain, et T. G. Clark, « Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis », Nature Genetics, janv. 2018.

  • M. Comisso, A. Hadchouel, J. de Blic, et M. Mirande, « Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity », The FEBS journal, mai 2018.
    Résumé : Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in MARS-related PAP are currently unknown. In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNAMet -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP.
    Mots-clés : aminoacylation kinetics, BDG, MARS, methionyl-tRNA synthetase, pulmonary alveolar proteinosis.

  • D. Couvin, A. Bernheim, C. Toffano-Nioche, M. Touchon, J. Michalik, B. Néron, E. P. C Rocha, G. Vergnaud, D. Gautheret, et C. Pourcel, « CRISPRCasFinder, an update of CRISRFinder, includes a portable version, enhanced performance and integrates search for Cas proteins », Nucleic Acids Research, mai 2018.
    Résumé : CRISPR (clustered regularly interspaced short palindromic repeats) arrays and their associated (Cas) proteins confer bacteria and archaea adaptive immunity against exogenous mobile genetic elements, such as phages or plasmids. CRISPRCasFinder allows the identification of both CRISPR arrays and Cas proteins. The program includes: (i) an improved CRISPR array detection tool facilitating expert validation based on a rating system, (ii) prediction of CRISPR orientation and (iii) a Cas protein detection and typing tool updated to match the latest classification scheme of these systems. CRISPRCasFinder can either be used online or as a standalone tool compatible with Linux operating system. All third-party software packages employed by the program are freely available. CRISPRCasFinder is available at https://crisprcas.i2bc.paris-saclay.fr.
    Mots-clés : BDG, LGBMB, MICROBIO, SSFA.

  • M. Crüsemann, R. Reher, I. Schamari, A. O. Brachmann, T. Ohbayashi, M. Kuschak, D. Malfacini, A. Seidinger, M. Pinto-Carbó, R. Richarz, T. Reuter, S. Kehraus, A. Hallab, M. Attwood, H. B. Schiöth, P. Mergaert, Y. Kikuchi, T. F. Schäberle, E. Kostenis, D. Wenzel, C. E. Müller, J. Piel, A. Carlier, L. Eberl, et G. M. König, « Heterologous Expression, Biosynthetic Studies, and Ecological Function of the Selective Gq-Signaling Inhibitor FR900359 », Angewandte Chemie (International Ed. in English), vol. 57, nᵒ 3, p. 836-840, janv. 2018.
    Résumé : The cyclic depsipeptide FR900359 (FR), isolated from the tropical plant Ardisia crenata, is a strong and selective inhibitor of Gq proteins, making it an indispensable pharmacological tool to study Gq-related processes, as well as a promising drug candidate. Gq inhibition is a novel mode of action for defense chemicals and crucial for the ecological function of FR, as shown by in vivo experiments in mice, its affinity to insect Gq proteins, and insect toxicity studies. The uncultured endosymbiont of A. crenata was sequenced, revealing the FR nonribosomal peptide synthetase (frs) gene cluster. We here provide a detailed model of FR biosynthesis, supported by in vitro enzymatic and bioinformatic studies, and the novel analogue AC-1, which demonstrates the flexibility of the FR starter condensation domains. Finally, expression of the frs genes in E. coli led to heterologous FR production in a cultivable, bacterial host for the first time.
    Mots-clés : biosynthesis, FR900359, G proteins, G proteins, Heterologous expression, MICROBIO, natural products, PBI.


  • V. Da Cunha, M. Gaia, A. Nasir, et P. Forterre, « Asgard archaea do not close the debate about the universal tree of life topology », PLOS Genetics, vol. 14, nᵒ 3, p. e1007215, mars 2018.

  • C. Dard-Dascot, D. Naquin, Y. d'Aubenton-Carafa, K. Alix, C. Thermes, et E. van Dijk, « Systematic comparison of small RNA library preparation protocols for next-generation sequencing », BMC genomics, vol. 19, nᵒ 1, p. 118, 2018.
    Résumé : BACKGROUND: Next-generation sequencing technologies have revolutionized the study of small RNAs (sRNAs) on a genome-wide scale. However, classical sRNA library preparation methods introduce serious bias, mainly during adapter ligation steps. Several types of sRNA including plant microRNAs (miRNA), piwi-interacting RNAs (piRNA) in insects, nematodes and mammals, and small interfering RNAs (siRNA) in insects and plants contain a 2'-O-methyl (2'-OMe) modification at their 3' terminal nucleotide. This inhibits 3' adapter ligation and makes library preparation particularly challenging. To reduce bias, the NEBNext kit (New England Biolabs) uses polyethylene glycol (PEG), the NEXTflex V2 kit (BIOO Scientific) uses both randomised adapters and PEG, and the novel SMARTer (Clontech) and CATS (Diagenode) kits avoid ligation altogether. Here we compared these methods with Illumina's classical TruSeq protocol regarding the detection of normal and 2' OMe RNAs. In addition, we modified the TruSeq and NEXTflex protocols to identify conditions that improve performance. RESULTS: Among the five kits tested with their respective standard protocols, the SMARTer and CATS kits had the lowest levels of bias but also had a strong formation of side products, and as a result performed relatively poorly with biological samples; NEXTflex detected the largest numbers of different miRNAs. The use of a novel type of randomised adapters called MidRand-Like (MRL) adapters and PEG improved the detection of 2' OMe RNAs both in the TruSeq as well as in the NEXTflex protocol. CONCLUSIONS: While it is commonly accepted that biases in sRNA library preparation protocols are mainly due to adapter ligation steps, the ligation-free protocols were not the best performing methods. Our modified versions of the TruSeq and NEXTflex protocols provide an improved tool for the study of 2' OMe RNAs.
    Mots-clés : 2’-O-methyl RNA, ANGE, Bias, CHERDIR, DBG, Library preparation, Next-generation sequencing, NGS, PF, Small RNA.

  • M. David, C. Lebrun, T. Duguet, F. Talmont, R. Beech, S. Orlowski, F. André, R. K. Prichard, et A. Lespine, « Structural model, functional modulation by ivermectin and tissue localization of Haemonchus contortus P-glycoprotein-13 », International Journal for Parasitology. Drugs and Drug Resistance, vol. 8, nᵒ 1, p. 145-157, avr. 2018.
    Résumé : Haemonchus contortus, one of the most economically important parasites of small ruminants, has become resistant to the anthelmintic ivermectin. Deciphering the role of P-glycoproteins in ivermectin resistance is desirable for understanding and overcoming this resistance. In the model nematode, Caenorhabditis elegans, P-glycoprotein-13 is expressed in the amphids, important neuronal structures for ivermectin activity. We have focused on its ortholog in the parasite, Hco-Pgp-13. A 3D model of Hco-Pgp-13, presenting an open inward-facing conformation, has been constructed by homology with the Cel-Pgp-1 crystal structure. In silico docking calculations predicted high affinity binding of ivermectin and actinomycin D to the inner chamber of the protein. Following in vitro expression, we showed that ivermectin and actinomycin D modulated Hco-Pgp-13 ATPase activity with high affinity. Finally, we found in vivo Hco-Pgp-13 localization in epithelial, pharyngeal and neuronal tissues. Taken together, these data suggest a role for Hco-Pgp-13 in ivermectin transport, which could contribute to anthelmintic resistance.
    Mots-clés : ABC transporters, B3S, Haemonchus contortus, Homology modeling, Ivermectin, LPSM, LSOD, Nematode, P-glycoprotein.


  • A. De Muyt, A. Pyatnitskaya, J. Andréani, L. Ranjha, C. Ramus, R. Laureau, A. Fernandez-Vega, D. Holoch, E. Girard, J. Govin, R. Margueron, Y. Couté, P. Cejka, R. Guérois, et V. Borde, « A meiotic XPF–ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation », Genes & Development, vol. 32, nᵒ 3-4, p. 283-296, févr. 2018.

  • Y. Dessaux et D. Faure, « Niche Construction and Exploitation by Agrobacterium: How to Survive and Face Competition in Soil and Plant Habitats », Berlin, Heidelberg: Springer Berlin Heidelberg, 2018.

  • Y. Dessaux et D. Faure, « Quorum Sensing and Quorum Quenching in Agrobacterium: A "Go/No Go System"? », Genes, vol. 9, nᵒ 4, avr. 2018.
    Résumé : The pathogen Agrobacterium induces gall formation on a wide range of dicotyledonous plants. In this bacteria, most pathogenicity determinants are borne on the tumour inducing (Ti) plasmid. The conjugative transfer of this plasmid between agrobacteria is regulated by quorum sensing (QS). However, processes involved in the disturbance of QS also occur in this bacteria under the molecular form of a protein, TraM, inhibiting the sensing of the QS signals, and two lactonases BlcC (AttM) and AiiB that degrade the acylhomoserine lactone (AHL) QS signal. In the model Agrobacteriumfabrum strain C58, several data, once integrated, strongly suggest that the QS regulation may not be reacting only to cell concentration. Rather, these QS elements in association with the quorum quenching (QQ) activities may constitute an integrated and complex “go/no go system” that finely controls the biologically costly transfer of the Ti plasmid in response to multiple environmental cues. This decision mechanism permits the bacteria to sense whether it is in a gall or not, in a living or decaying tumor, in stressed plant tissues, etc. In this scheme, the role of the lactonases selected and maintained in the course of Ti plasmid and agrobacterial evolution appears to be pivotal.
    Mots-clés : (p)ppGpp, Agrobacterium, GABA, lactonase, MICROBIO, PBI, proline, quorum quenching, quorum sensing, Ti plasmid.

  • T. Di Mattia, L. P. Wilhelm, S. Ikhlef, C. Wendling, D. Spehner, Y. Nominé, F. Giordano, C. Mathelin, G. Drin, C. Tomasetto, et F. Alpy, « Identification of MOSPD2, a novel scaffold for endoplasmic reticulum membrane contact sites », EMBO reports, vol. 19, nᵒ 7, juill. 2018.
    Résumé : Membrane contact sites are cellular structures that mediate interorganelle exchange and communication. The two major tether proteins of the endoplasmic reticulum (ER), VAP-A and VAP-B, interact with proteins from other organelles that possess a small VAP-interacting motif, named FFAT [two phenylalanines (FF) in an acidic track (AT)]. In this study, using an unbiased proteomic approach, we identify a novel ER tether named motile sperm domain-containing protein 2 (MOSPD2). We show that MOSPD2 possesses a Major Sperm Protein (MSP) domain which binds FFAT motifs and consequently allows membrane tethering in vitro MOSPD2 is an ER-anchored protein, and it interacts with several FFAT-containing tether proteins from endosomes, mitochondria, or Golgi. Consequently, MOSPD2 and these organelle-bound proteins mediate the formation of contact sites between the ER and endosomes, mitochondria, or Golgi. Thus, we characterized here MOSPD2, a novel tethering component related to VAP proteins, bridging the ER with a variety of distinct organelles.
    Mots-clés : BIOCELL, COAST, endoplasmic reticulum, ER–organelle contact, FFAT motif, membrane contact site, VAP proteins.

  • G. M. Dias, A. Bidault, P. Le Chevalier, G. Choquet, C. Der Sarkissian, L. Orlando, C. Medigue, V. Barbe, S. Mangenot, C. C. Thompson, F. L. Thompson, A. Jacq, V. Pichereau, et C. Paillard, « Vibrio tapetis Displays an Original Type IV Secretion System in Strains Pathogenic for Bivalve Molluscs », Frontiers in Microbiology, vol. 9, p. 227, 2018.
    Résumé : The Brown Ring Disease (BRD) caused high mortality rates since 1986 in the Manila clamVenerupis philippinarumintroduced and cultured in Western Europe from the 1970s. The causative agent of BRD is a Gram-Negative bacterium,Vibrio tapetis, which is also pathogenic to fish. Here we report the first assembly of the complete genome ofV. tapetisCECT4600T, together with the genome sequences of 16 additional strains isolated across a broad host and geographic range. Our extensive genome dataset allowed us to describe the pathogen pan- and core genomes and to identify putative virulence factors. TheV. tapetiscore genome consists of 3,352 genes, including multiple potential virulence factors represented by haemolysins, transcriptional regulators, Type I restriction modification system, GGDEF domain proteins, several conjugative plasmids, and a Type IV secretion system. Future research on the coevolutionary arms race betweenV. tapetisvirulence factors and host resistance mechanisms will improve our understanding of how pathogenicity develops in this emerging pathogen.
    Mots-clés : BDG, comparative genomics, core genome, pangenome, pathogenicity, SRRB, T4SS, Venerupis philippinarum, Vibrio tapetis.


  • A. Doerflinger, N. N. Quang, E. Gravel, G. Pinna, M. Vandamme, F. Ducongé, et E. Doris, « Biotin-functionalized targeted polydiacetylene micelles », Chemical Communications, 2018.

  • A. Dreinert, A. Wolf, T. Mentzel, B. Meunier, et M. Fehr, « The cytochrome bc1 complex inhibitor Ametoctradin has an unusual binding mode », Biochimica et Biophysica Acta (BBA) - Bioenergetics, vol. 1859, nᵒ 8, p. 567-576, avr. 2018.
    Résumé : Ametoctradin is an agricultural fungicide that selectively inhibits the cytochrome bc1 complex of oomycetes. Previous spectrophotometric studies using the purified cytochrome bc1 complex from Pythium sp. showed that Ametoctradin binds to the Qo-site of the enzyme. However, as modeling studies suggested a binding mode like that of the substrate ubiquinol, the possibility for a dual Qo- and Qi-site binding mode was left open. In this work, binding studies and enzyme assays with mitochondrial membrane preparations from Pythium sp. and an S. cerevisiae strain with a modified Qi-site were used to investigate further the binding mode of Ametoctradin. The results obtained argue that the compound could bind to both the Qo- and Qi-sites of the cytochrome bc1 complex and that its position or binding pose in the Qi-site differs from that of Cyazofamid and Amisulbrom, the two Qi-site-targeting, anti-oomycetes compounds. Furthermore, the data support the argument that Ametoctradin prefers binding to the reduced cytochrome bc1 complex. Thus, Ametoctradin has an unusual binding mode and further studies with this compound may offer the opportunity to better understand the catalytic cycle of the cytochrome bc1 complex.
    Mots-clés : Ametoctradin, Amisulbrom, BIOCELL, BIOMIT, Cyazofamid, Cytochrome bc(1) complex, Initium, Oomycetes, Respiration inhibitor, Respiratory complex III.

  • D. Drubay, D. Gautheret, et S. Michiels, « A benchmark study of scoring methods for non-coding mutations », Bioinformatics (Oxford, England), janv. 2018.
    Résumé : Motivation: Detailed knowledge of coding sequences has led to different candidate models for pathogenic variant prioritization. Several deleteriousness scores have been proposed for the non-coding part of the genome, but no large-scale comparison has been realized to date to assess their performance. Results: We compared the leading scoring tools (CADD, FATHMM-MKL, Funseq2 and GWAVA) and some recent competitors (DANN, SNP and SOM scores) for their ability to discriminate assumed pathogenic variants from assumed benign variants (using the ClinVar, COSMIC and 1000 genomes project databases). Using the ClinVar benchmark, CADD was the best tool for detecting the pathogenic variants that are mainly located in protein coding gene regions. Using the COSMIC benchmark, FATHMM-MKL, GWAVA and SOMliver outperformed the other tools for pathogenic variants that are typically located in lincRNAs, pseudogenes, and other parts of the non-coding genome. However, all tools had low precision, which could potentially be improved by future non-coding genome feature discoveries. These results may have been influenced by the presence of potential benign variants in the COSMIC database. The development of a gold standard as consistent as ClinVar for these regions will be necessary to confirm our tool ranking. Availability and Implementation: The Snakemake, C ++ and R codes are freely available from https://github.com/Oncostat/BenchmarkNCVTools and supported on Linux. Contact: damien.drubay@gustaveroussy.fr. Supplementary information: Supplementary results are available at Bioinformatics online.
    Mots-clés : DBG, SSFA.

  • G. Dubeaux, J. Neveu, E. Zelazny, et G. Vert, « Metal Sensing by the IRT1 Transporter-Receptor Orchestrates Its Own Degradation and Plant Metal Nutrition », Molecular Cell, vol. 69, nᵒ 6, p. 953-964.e5, mars 2018.
    Résumé : Plant roots forage the soil for iron, the concentration of which can be dramatically lower than those needed for growth. Soil iron uptake uses the broad metal spectrum IRT1 transporter that also transports zinc, manganese, cobalt, and cadmium. Sophisticated iron-dependent transcriptional regulatory mechanisms allow plants to tightly control the abundance of IRT1, ensuring optimal absorption of iron. Here, we uncover that IRT1 acts as a transporter and receptor (transceptor), directly sensing excess of its non-iron metal substrates in the cytoplasm, to regulate its own degradation. Direct metal binding to a histidine-rich stretch in IRT1 triggers its phosphorylation by the CIPK23 kinase and facilitates the subsequent recruitment of the IDF1 E3 ligase. CIPK23-driven phosphorylation and IDF1-mediated lysine-63 polyubiquitination are jointly required for efficient endosomal sorting and vacuolar degradation of IRT1. Thus, IRT1 directly senses elevated non-iron metal concentrations and integrates multiple substrate-dependent regulations to optimize iron uptake and protect plants from highly reactive metals.
    Mots-clés : Arabidopsis, BIOCELL, degradation, metal homeostasis, phosphorylation, plant, receptor, sensing, transceptor, transporter, UBINET, ubiquitin.

  • A. Durand, M. - L. Bourbon, A. - S. Steunou, B. Khalfaoui-Hassani, C. Legrand, A. Guitton, C. Astier, et S. Ouchane, « Biogenesis of the bacterial cbb3 cytochrome c oxidase: Active subcomplexes support a sequential assembly model », The Journal of Biological Chemistry, vol. 293, nᵒ 3, p. 808-818, janv. 2018.
    Résumé : The cbb3 oxidase has a high affinity for oxygen and is required for growth of bacteria, including pathogens, in oxygen-limited environments. However, the assembly of this oxidase is poorly understood. Most cbb3 are composed of four subunits: the catalytic CcoN subunit, the two cytochrome c subunits (CcoO and CcoP) involved in electron transfer, and the small CcoQ subunit with an unclear function. Here, we address the role of these four subunits in cbb3 biogenesis in the purple bacterium Rubrivivax gelatinosus Analyses of membrane proteins from different mutants revealed the presence of active CcoNQO and CcoNO subcomplexes and also showed that the CcoP subunit is not essential for their assembly. However, CcoP was required for the oxygen reduction activity in the absence of CcoQ. We also found that CcoQ is dispensable for forming an active CcoNOP subcomplex in membranes. CcoNOP exhibited oxygen reductase activity, indicating that the cofactors (hemes b and copper for CcoN and cytochromes c for CcoO and CcoP) were present within the subunits. Finally, we discovered the presence of a CcoNQ subcomplex and showed that CcoN is the required anchor for the assembly of the full CcoNQOP complex. On the basis of these findings, we propose a sequential assembly model in which the CcoQ subunit is required for the early maturation step: CcoQ first associates with CcoN before the CcoNQ-CcoO interaction. CcoP associates to CcoNQO subcomplex in the late maturation step, and once the CcoNQOP complex is fully formed, CcoQ is released for degradation by the FtsH protease. This model could be conserved in other bacteria, including the pathogenic bacteria lacking the assembly factor CcoH as in R. gelatinosus.
    Mots-clés : BACADA, bacteria, cbb3 cytochrome c oxidase biogenesis, cytochrome oxidase, Membrane protein, MICROBIO.

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