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Accueil > Séminaires

Département Biochimie, Biophysique et Biologie Structurale

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Agenda

  • Mardi 28 novembre 11:00-12:00 - Prof. Jurgen Sygusch - Professeur titulaire, Biochimie, Université de Montréal

    Aspects mécanistiques et fonctions ’moonlighting’ de l’enzyme glycolytique aldolase

    Résumé : La fructose-bis phosphate aldolase est un enzyme essentiel de la glycolyse et des fonctions cellulaires. L’enzyme démontre une stéréospécificité exquise envers son substrat. Dans la direction de la gluconéogenèse, l’enzyme catalyse la synthèse de son substrat chiral à partir des réactifs achiraux. Le mécanisme réactionnel préconisé par l’enzyme qui produira le diastéréoisomère, fructose-bisphosphate, à partir des triose-Ps achiraux sera le sujet de la conférence. Les enzymes glycolytiques sont bien connus pour leurs rôles de ‘moonlighting’ où il interagit avec d’autres protéines intracellulaires en modifiant leurs fonctions. Dans le cas de l’aldolase, l’enzyme exerce un rôle important dans le maintien du cytosquelette et son inhibition a un effet fortement inhibiteur sur la croissance des cellules cancérigènes. Comment l’inhibition de l’enzyme aldolase se traduit-elle par l’apoptose des cellules cancérigènes sera également le sujet de la conférence.

    Lieu : Salle Lederer - Bâtiment 430
    Campus d’Orsay


  • Mercredi 29 novembre 10:30-11:30 - Dr Sonia LONGHI - Lab. AFMB, CNRS & Aix-Marseille University, Marseille, France

    The interplay between order and disorder in the replicative complex of paramyxoviruses

    Résumé : In the course of the structural characterization of the nucleoproteins (N) and phosphoproteins (P) from three paramyxoviruses (e.g. measles, Nipah and Hendra virus) we discovered that they contain long disordered regions. The N and P proteins from these viruses thus provide an excellent model system to study the functional impact of disordered motifs. The non-segmented, single-stranded RNA genome of these paramyxoviruses is encapsidated by the nucleoprotein (N) within a helical nucleocapsid. Transcription and replication are carried out onto this ribonucleoproteic complex by the viral RNA dependent RNA polymerase that consists of a complex between the large protein (L) and the phosphoprotein (P). The P protein serves as an essential polymerase co-factor as it allows recruitment of L onto the nucleocapsid template. Tethering of L relies on the interaction between the C-terminal X domain (PXD) of the P protein and the C- terminal, intrinsically disordered domain (NTAIL) of N. This latter is disordered not only in isolation but also in the context of the nucleocapsid, being partly exposed at the surface of this latter. Within NTAIL, a short motif, serving as molecular recognition element (MoRE), has been identified and the mechanisms of its interaction with PXD thoroughly investigated. In its free from, the MoRE is partly pre-configured as an α-helix. Binding to PXD triggers stable α-helical folding of this motif, while the majority of NTAIL remains “fuzzy”. Beyond PXD, measles virus NTAIL also binds the major inducible heat shock protein 70 (hsp70). Although NTAIL binds hsp70 through the same motif involved in binding to PXD, the binding mechanisms are not the same, which constitutes an illustrative example of partner-mediated polymorphism of an intrinsically disordered protein and of the relative insensitiveness of the bound structure to the pre-recognition state.
    In my talk, I will focus on measles virus NTAIL and will summarize the main results we obtained so far. In particular, I will focus on the mechanistic and functional aspects of the interactions established by NTAIL and will highlight the functional implications of disorder for viral transcription and replication.
    Choice of five selected references
    1. Longhi et al (2017) Cell. Mol. Life Sci. 74, 3091–3118
    2. Bloyet LM et al (2016) Plos Pathogens 12(12):e1006058.
    3. Longhi S. (2015) FEBS Lett. 589, 2649-59.
    4. Dosnon et al (2015) ACS Chem. Biol. 10, 795−802
    5. Habchi J et al (2014) Chem. Rev. 114, 6561-88.

    Lieu : Bibliothèque - Bâtiment 34, Campus de Gif


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