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Accueil > Départements > Biochimie, Biophysique et Biologie Structurale > Stéphane BRESSANELLI : Interactions et mécanismes d’assemblage des protéines et des peptides

Publications de l’équipe


  • E. Baquero, A. A. Albertini, H. Raux, A. Abou‐Hamdan, E. Boeri‐Erba, M. Ouldali, L. Buonocore, J. K. Rose, J. Lepault, S. Bressanelli, et Y. Gaudin, « Structural intermediates in the fusion‐associated transition of vesiculovirus glycoprotein », The EMBO Journal, vol. 36, nᵒ 5, p. 679-692, mars 2017.
    Mots-clés : B3S, conformational change, glycoprotein, IMAPP, intermediate structures, membrane fusion, RHABDO, Vesiculovirus, VIRO, VIROEM.

  • S. Fieulaine, R. Alves de Sousa, L. Maigre, K. Hamiche, M. Alimi, J. - M. Bolla, A. Taleb, A. Denis, J. - M. Pagès, I. Artaud, T. Meinnel, et C. Giglione, « Corrigendum: A unique peptide deformylase platform to rationally design and challenge novel active compounds », Scientific Reports, vol. 7, p. 39365, janv. 2017.

  • R. Grzela, J. Nusbaum, S. Fieulaine, F. Lavecchia, W. V. Bienvenut, C. Dian, T. Meinnel, et C. Giglione, « The C-terminal residue of phage Vp16 PDF, the smallest peptide deformylase, acts as an offset element locking the active conformation », Scientific Reports, vol. 7, nᵒ 1, p. 11041, 2017.
    Résumé : Prokaryotic proteins must be deformylated before the removal of their first methionine. Peptide deformylase (PDF) is indispensable and guarantees this mechanism. Recent metagenomics studies revealed new idiosyncratic PDF forms as the most abundant family of viral sequences. Little is known regarding these viral PDFs, including the capacity of the corresponding encoded proteins to ensure deformylase activity. We provide here the first evidence that viral PDFs, including the shortest PDF identified to date, Vp16 PDF, display deformylase activity in vivo, despite the absence of the key ribosome-interacting C-terminal region. Moreover, characterization of phage Vp16 PDF underscores unexpected structural and molecular features with the C-terminal Isoleucine residue significantly contributing to deformylase activity both in vitro and in vivo. This residue fully compensates for the absence of the usual long C-domain. Taken together, these data elucidate an unexpected mechanism of enzyme natural evolution and adaptation within viral sequences.
    Mots-clés : B3S, DBG, IMAPP, PROMTI.

  • E. Karakas, C. Taveneau, S. Bressanelli, M. Marchi, B. Robert, et S. Abel, « Derivation of original RESP atomic partial charges for MD simulations of the LDAO surfactant with AMBER: applications to a model of micelle and a fragment of the lipid kinase PI4KA », Journal of Biomolecular Structure and Dynamics, vol. 35, nᵒ 1, p. 159-181, janv. 2017.
    Mots-clés : Amber, B3S, Dimethylamines, fluorescence spectroscopy, IMAPP, LBMS, LDAO surfactant, lipid kinase PI4KA, Lipids, MD simulation, micelle, Micelles, Minor Histocompatibility Antigens, Molecular Conformation, Molecular Dynamics Simulation, molecular modeling, Phosphotransferases (Alcohol Group Acceptor), Protein Binding, Proteins, Static Electricity, Surface-Active Agents.

  • P. K. Mandal, D. Shukla, V. Govind, Y. Boulard, et L. Ersland, « Glutathione Conformations and Its Implications for in vivo Magnetic Resonance Spectroscopy », Journal of Alzheimer's disease: JAD, 2017.
    Résumé : Glutathione (GSH) is a major antioxidant in humans that is involved in the detoxification of reactive radicals and peroxides. The molecular structural conformations of GSH depend on the surrounding micro-environment, and it has been experimentally evaluated using NMR and Raman spectroscopic techniques as well as by molecular dynamics simulation studies. The converging report indicates that GSH exists mainly in two major conformations, i.e., "extended" and "folded". The NMR-derived information on the GSH conformers is essential to obtain optimal acquisition parameters in in vivo MRS experiments targeted for GSH detection. To further investigate the implications of GSH conformers in in vivo MRS studies and their relative proportions in healthy and pathological conditions, a multi-center clinical research study is necessary with a common protocol for GSH detection and quantification.
    Mots-clés : Antioxidant, B3S, Brain, conformation, Glutathione, IMAPP, Magnetic Resonance Spectroscopy, molecular dynamics, nuclear magnetic resonance.

  • T. Tubiana, Y. Boulard, et S. Bressanelli, « Dynamics and asymmetry in the dimer of the norovirus major capsid protein », PloS One, vol. 12, nᵒ 7, p. e0182056, 2017.
    Résumé : Noroviruses are the major cause of non-bacterial acute gastroenteritis in humans and livestock worldwide, despite being physically among the simplest animal viruses. The icosahedral capsid encasing the norovirus RNA genome is made of 90 dimers of a single ca 60-kDa polypeptide chain, VP1, arranged with T = 3 icosahedral symmetry. Here we study the conformational dynamics of this main building block of the norovirus capsid. We use molecular modeling and all-atom molecular dynamics simulations of the VP1 dimer for two genogroups with 50% sequence identity. We focus on the two points of flexibility in VP1 known from the crystal structure of the genogroup I (GI, human) capsid and from subsequent cryo-electron microscopy work on the GII capsid (also human). First, with a homology model of the GIII (bovine) VP1 dimer subjected to simulated annealing then classical molecular dynamics simulations, we show that the N-terminal arm conformation seen in the GI crystal structure is also favored in GIII VP1 but depends on the protonation state of critical residues. Second, simulations of the GI dimer show that the VP1 spike domain will not keep the position found in the GII electron microscopy work. Our main finding is a consistent propensity of the VP1 dimer to assume prominently asymmetric conformations. In order to probe this result, we obtain new SAXS data on GI VP1 dimers. These data are not interpretable as a population of symmetric dimers, but readily modeled by a highly asymmetric dimer. We go on to discuss possible implications of spontaneously asymmetric conformations in the successive steps of norovirus capsid assembly. Our work brings new lights on the surprising conformational range encoded in the norovirus major capsid protein.
    Mots-clés : B3S, IMAPP.


  • A. Akil, J. Peng, M. Omrane, C. Gondeau, C. Desterke, M. Marin, H. Tronchère, C. Taveneau, S. Sar, P. Briolotti, S. Benjelloun, A. Benjouad, P. Maurel, V. Thiers, S. Bressanelli, D. Samuel, C. Bréchot, et A. Gassama-Diagne, « Septin 9 induces lipid droplets growth by a phosphatidylinositol-5-phosphate and microtubule-dependent mechanism hijacked by HCV », Nature Communications, vol. 7, p. 12203, juill. 2016.

  • A. Breiman, S. Fieulaine, T. Meinnel, et C. Giglione, « The intriguing realm of protein biogenesis: Facing the green co-translational protein maturation networks », Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, vol. 1864, nᵒ 5, p. 531-550, 2016.
    Mots-clés : B3S, Co-translational folding, Co-translational modifications, Co-translational targeting, DBG, IMAPP, Macromolecular Substances, Plants, PROMTI, Protein Biosynthesis, Protein Folding, Protein Processing, Post-Translational, Proteolysis, Ribosome, Ribosome-associated protein biogenesis factors, Ribosomes.

  • S. Fieulaine, R. Alves de Sousa, L. Maigre, K. Hamiche, M. Alimi, J. - M. Bolla, A. Taleb, A. Denis, J. - M. Pagès, I. Artaud, T. Meinnel, et C. Giglione, « A unique peptide deformylase platform to rationally design and challenge novel active compounds », Scientific Reports, vol. 6, p. 35429, oct. 2016.

  • G. Klein, S. Devineau, J. C. Aude, Y. Boulard, H. Pasquier, J. Labarre, S. Pin, et J. P. Renault, « Interferences of Silica Nanoparticles in Green Fluorescent Protein Folding Processes », Langmuir: the ACS journal of surfaces and colloids, vol. 32, nᵒ 1, p. 195-202, 2016.
    Résumé : We investigated the relationship between unfolded proteins, silica nanoparticles and chaperonin to determine whether unfolded proteins could stick to silica surfaces and how this process could impair heat shock protein activity. The HSP60 catalyzed green fluorescent protein (GFP) folding was used as a model system. The adsorption isotherms and adsorption kinetics of denatured GFP were measured, showing that denaturation increases GFP affinity for silica surfaces. This affinity is maintained even if the surfaces are covered by a protein corona and allows silica NPs to interfere directly with GFP folding by trapping it in its unstructured state. We determined also the adsorption isotherms of HSP60 and its chaperonin activity once adsorbed, showing that SiO2 NP can interfere also indirectly with protein folding through chaperonin trapping and inhibition. This inhibition is specifically efficient when NPs are covered first with a layer of unfolded proteins. These results highlight for the first time the antichaperonin activity of silica NPs and ask new questions about the toxicity of such misfolded proteins/nanoparticles assembly toward cells.
    Mots-clés : B3S, DBG, Green Fluorescent Proteins, IMAPP, Nanoparticles, PEPS, Protein Folding, Silicon Dioxide.

  • G. Klein, C. Mathé, M. Biola-Clier, S. Devineau, E. Drouineau, E. Hatem, L. Marichal, B. Alonso, J. - C. Gaillard, G. Lagniel, J. Armengaud, M. Carrière, S. Chédin, Y. Boulard, S. Pin, J. - P. Renault, J. - C. Aude, et J. Labarre, « RNA-binding proteins are a major target of silica nanoparticles in cell extracts », Nanotoxicology, vol. 10, nᵒ 10, p. 1555-1564, 2016.
    Résumé : Upon contact with biological fluids, nanoparticles (NPs) are readily coated by cellular compounds, particularly proteins, which are determining factors for the localization and toxicity of NPs in the organism. Here, we improved a methodological approach to identify proteins that adsorb on silica NPs with high affinity. Using large-scale proteomics and mixtures of soluble proteins prepared either from yeast cells or from alveolar human cells, we observed that proteins with large unstructured region(s) are more prone to bind on silica NPs. These disordered regions provide flexibility to proteins, a property that promotes their adsorption. The statistical analyses also pointed to a marked overrepresentation of RNA-binding proteins (RBPs) and of translation initiation factors among the adsorbed proteins. We propose that silica surfaces, which are mainly composed of Si-O(-) and Si-OH groups, mimic ribose-phosphate molecules (rich in -O(-) and -OH) and trap the proteins able to interact with ribose-phosphate containing molecules. Finally, using an in vitro assay, we showed that the sequestration of translation initiation factors by silica NPs results in an inhibition of the in vitro translational activity. This result demonstrates that characterizing the protein corona of various NPs would be a relevant approach to predict their potential toxicological effects.
    Mots-clés : B3S, BIM, DBG, IMAPP, intrinsically disordered protein, PEPS, Protein corona, proteomics, RNA binding protein, silica nanoparticles.

  • D. Law-Hine, M. Zeghal, S. Bressanelli, D. Constantin, et G. Tresset, « Identification of a major intermediate along the self-assembly pathway of an icosahedral viral capsid by using an analytical model of a spherical patch », Soft Matter, vol. 12, nᵒ 32, p. 6728-6736, 2016.


  • M. Ayach et S. Bressanelli, « Crystallization of mutants of Turnip yellow mosaic virus protease/ubiquitin hydrolase designed to prevent protease self-recognition », Acta Crystallographica. Section F, Structural Biology Communications, vol. 71, nᵒ Pt 4, p. 405-408, 2015.
    Résumé : Processing of the polyprotein of Turnip yellow mosaic virus is mediated by the protease PRO. PRO cleaves at two places, one of which is at the C-terminus of the PRO domain of another polyprotein molecule. In addition to this processing activity, PRO possesses an ubiquitin hydrolase (DUB) activity. The crystal structure of PRO has previously been reported in its polyprotein-processing mode with the C-terminus of one PRO inserted into the catalytic site of the next PRO, generating PRO polymers in the crystal packing of the trigonal space group. Here, two mutants designed to disrupt specific PRO-PRO interactions were generated, produced and purified. Crystalline plates were obtained by seeding and cross-seeding from initial `sea urchin'-like microcrystals of one mutant. The plates diffracted to beyond 2 Å resolution at a synchrotron source and complete data sets were collected for the two mutants. Data processing and analysis indicated that both mutant crystals belonged to the same monoclinic space group, with two molecules of PRO in the asymmetric unit.
    Mots-clés : Amino Acid Sequence, B3S, Crystallization, Hydrolases, IMAPP, Molecular Sequence Data, Mutation, self-processing viral cysteine proteinase, Tymovirus, Ubiquitin, ubiquitin hydrolase, Ubiquitin-Specific Proteases.

  • E. Baquero, A. A. Albertini, H. Raux, L. Buonocore, J. K. Rose, S. Bressanelli, et Y. Gaudin, « Structure of the Low pH Conformation of Chandipura Virus G Reveals Important Features in the Evolution of the Vesiculovirus Glycoprotein », PLOS Pathogens, vol. 11, nᵒ 3, p. e1004756, mars 2015.
    Mots-clés : B3S, Evolution, Molecular, Humans, Hydrogen-Ion Concentration, IMAPP, Nucleocapsid, Protein Structure, Tertiary, RHABDO, Vesiculovirus, Viral Fusion Proteins, VIRO.

  • S. Bressanelli, « Kickstarting a viral RNA polymerase », Science, vol. 347, nᵒ 6223, p. 715-716, févr. 2015.

  • C. Giglione, S. Fieulaine, et T. Meinnel, « N-terminal protein modifications: Bringing back into play the ribosome », Biochimie, vol. 114, p. 134-146, 2015.
    Mots-clés : Amidohydrolases, Amino Acid Sequence, Animals, B3S, Co-translational modifications, DBG, Humans, IMAPP, Methionine aminopeptidase, Methionyl Aminopeptidases, Molecular Sequence Data, N-myristoyltransferase, N-terminal, N-α-acetyltransferase, Peptide deformylase, PROMTI, Protein Biosynthesis, Protein Processing, Post-Translational, Ribosomes.

  • C. Langlois, S. Ramboarina, A. Cukkemane, I. Auzat, B. Chagot, B. Gilquin, A. Ignatiou, I. Petitpas, E. Kasotakis, M. Paternostre, H. E. White, E. V. Orlova, M. Baldus, P. Tavares, et S. Zinn-Justin, « Bacteriophage SPP1 Tail Tube Protein Self-assembles into β-Structure-rich Tubes », Journal of Biological Chemistry, vol. 290, nᵒ 6, p. 3836-3849, févr. 2015.
    Mots-clés : Amino Acid Sequence, B3S, Bacteriophage, Bacteriophages, Electron Microscopy, Fourier Transform IR (FTIR), IMAPP, INTGEN, Molecular Sequence Data, PHAG+, Protein Folding, Protein Structure, Tertiary, Solid State NMR, Tail Tube, Tertiary Structure, Viral Proteins, Virion, VIRO, Virus Assembly.

  • D. Law-Hine, A. K. Sahoo, V. Bailleux, M. Zeghal, S. Prevost, P. K. Maiti, S. Bressanelli, D. Constantin, et G. Tresset, « Reconstruction of the Disassembly Pathway of an Icosahedral Viral Capsid and Shape Determination of Two Successive Intermediates », The Journal of Physical Chemistry Letters, vol. 6, nᵒ 17, p. 3471-3476, sept. 2015.

  • T. Michon, J. Sturgis, et S. Bressanelli, « Ingénierie des protéines : construire en 3D avec des protéines », in Synthèse 2014, Micro et Nanotechnologies : Avancées, tendances et perspectives, Observatoire des Micro et NanoTechnologies., 2015, p. 40-42.

  • N. Scrima, J. Lepault, Y. Boulard, D. Pasdeloup, S. Bressanelli, et S. Roche, « Insights into herpesvirus tegument organization from structural analyses of the 970 central residues of HSV-1 UL36 protein », The Journal of Biological Chemistry, vol. 290, nᵒ 14, p. 8820-8833, 2015.
    Résumé : The tegument of all herpesviruses contains a capsid-bound large protein that is essential for multiple viral processes, including capsid transport, decapsidation at the nuclear pore complex, particle assembly, and secondary envelopment, through mechanisms that are still incompletely understood. We report here a structural characterization of the central 970 residues of this protein for herpes simplex virus type 1 (HSV-1 UL36, 3164 residues). This large fragment is essentially a 34-nm-long monomeric fiber. The crystal structure of its C terminus shows an elongated domain-swapped dimer. Modeling and molecular dynamics simulations give a likely molecular organization for the monomeric form and extend our findings to alphaherpesvirinae. Hence, we propose that an essential feature of UL36 is the existence in its central region of a stalk capable of connecting capsid and membrane across the tegument and that the ability to switch between monomeric and dimeric forms may help UL36 fulfill its multiple functions.
    Mots-clés : Amino Acid Sequence, B3S, Cell Line, Transformed, Crystal Structure, Dimerization, Herpesvirus, Herpesvirus 1, Human, HSV1, Humans, IMAPP, Molecular Sequence Data, Protein Conformation, Sequence Homology, Amino Acid, Structural Biology, Tegument, ul36, Viral Proteins, VIRO, VIROEM, Virus Assembly, Virus Structure, vp1/2.

  • J. Stojko, S. Fieulaine, S. Petiot-Bécard, A. Van Dorsselaer, T. Meinnel, C. Giglione, et S. Cianférani, « Ion mobility coupled to native mass spectrometry as a relevant tool to investigate extremely small ligand-induced conformational changes », Analyst, vol. 140, nᵒ 21, p. 7234-7245, 2015.
    Mots-clés : Amidohydrolases, Anti-Bacterial Agents, Arabidopsis, B3S, Binding, Competitive, Buffers, Crystallography, X-Ray, DBG, IMAPP, Ions, Kinetics, Ligands, Mass Spectrometry, PROMTI, Protein Binding, Protein Conformation, Proteins.

  • C. Taveneau, K. Blondeau, et S. Bressanelli, « Definition and expression in E. coli of large fragments from the human lipid kinase phosphatidylinositol 4-kinase type III alpha, and purification of a 1100-residue N-terminal module », Protein Expression and Purification, vol. 114, p. 121-127, 2015.

  • C. Valéry, S. Deville-Foillard, C. Lefebvre, N. Taberner, P. Legrand, F. Meneau, C. Meriadec, C. Delvaux, T. Bizien, E. Kasotakis, C. Lopez-Iglesias, A. Gall, S. Bressanelli, M. - H. Le Du, M. Paternostre, et F. Artzner, « Atomic view of the histidine environment stabilizing higher-pH conformations of pH-dependent proteins », Nature Communications, vol. 6, p. 7771, juill. 2015.
    Mots-clés : B3S, Crystallography, X-Ray, Histidine, Hydrogen-Ion Concentration, IMAPP, INTGEN, LBMS, Models, Molecular, Nanotubes, Peptide, Optical Imaging, Protein Conformation, Protein Structure, Secondary, Spectroscopy, Fourier Transform Infrared, Spectrum Analysis, Raman, Triptorelin Pamoate.
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Publications avant 2015

  1. Tassali, N. ; Kotera, N. ; Boutin, C. ; Léonce, E. ; Boulard, Y. ; Rousseau, B. ; Dubost, E. ; Taran, F. ; Brotin, T. ; Dutasta, J.-P. ; Berthault, P. Smart Detection of Toxic Metal Ions, Pb2+ and Cd2+, Using a 129Xe NMR-Based Sensor. Anal. Chem. 2014, 86 (3), 1783–1788.
  2. Rieille, N. ; Bressanelli, S. ; Freire, C. C. ; Arcioni, S. ; Gern, L. ; Péter, O. ; Voordouw, M. J. Prevalence and Phylogenetic Analysis of Tick-Borne Encephalitis Virus (TBEV) in Field-Collected Ticks (Ixodes Ricinus) in Southern Switzerland. Parasit Vectors 2014, 7 (1), 443.
  3. Harak, C. ; Radujkovic, D. ; Taveneau, C. ; Reiss, S. ; Klein, R. ; Bressanelli, S. ; Lohmann, V. Mapping of Functional Domains of the Lipid Kinase Phosphatidylinositol 4-Kinase Type III Alpha Involved in Enzymatic Activity and Hepatitis C Virus Replication. J. Virol. 2014, 88 (17), 9909–9926.
  4. Gobeaux, F. ; Tarabout, C. ; Fay, N. ; Meriadec, C. ; Ligeti, M. ; Buisson, D.-A. ; Cintrat, J.-C. ; Artzner, F. ; Paternostre, M. Directing Peptide Crystallization through Curvature Control of Nanotubes. J. Pept. Sci. 2014, 20 (7), 508–516.
  5. Fieulaine, S. ; Desmadril, M. ; Meinnel, T. ; Giglione, C. Understanding the Highly Efficient Catalysis of Prokaryotic Peptide Deformylases by Shedding Light on the Determinants Specifying the Low Activity of the Human Counterpart. Acta Cryst. D 2014, 70 (Pt 2), 242–252.
  6. Duriez, M. ; Thouard, A. ; Bressanelli, S. ; Rossignol, J.-M. ; Sitterlin, D. Conserved Aromatic Residues of the Hepatitis B Virus Precore Propeptide Are Involved in a Switch between Distinct Dimeric Conformations and Essential in the Formation of Heterocapsids. Virology 2014, 462-463C, 273–282.
  7. Dubost, E. ; Dognon, J.-P. ; Rousseau, B. ; Milanole, G. ; Dugave, C. ; Boulard, Y. ; Léonce, E. ; Boutin, C. ; Berthault, P. Understanding a Host-Guest Model System through ¹²⁹Xe NMR Spectroscopic Experiments and Theoretical Studies. Angew. Chem. Int. Ed. Engl. 2014, 53 (37), 9837–9840.
  8. Caillet-Saguy, C. ; Lim, S. P. ; Shi, P.-Y. ; Lescar, J. ; Bressanelli, S. Polymerases of Hepatitis C Viruses and Flaviviruses : Structural and Mechanistic Insights and Drug Development. Antiviral Res. 2014, 105, 8–16.

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