Structural Dynamics of the C-terminal X Domain of Nipah and Hendra Viruses Controls the Attachment to the C-terminal Tail of the Nucleocapsid Protein

Autor: Jean-Marie Bourhis, Filip Yabukarski, Guillaume Communie, Robert Schneider, Valentina A. Volchkova, Mickaël Frénéat, Francine C. Gérard, Corinne Ducournau, Caroline Mas, Nicolas Tarbouriech, Malene Ringkjøbing Jensen, Viktor E. Volchkov, Martin Blackledge, Marc Jamin
Přispěvatelé: Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Structural Biology Grenoble (ISBG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), the Fond de la Recherche Médicale (FRM) (grant 'Equipe 2017' DEQ20170336754), the FINOVI Fundation, ANR-12-BSV8-0025,NNViPol,Structure et fonction de la machine de transcription et réplication des virus à ARN non-segmenté de polarité négative(2012), ANR-18-CE11-0014,NiPah-C,Structure et fonctions de la protéine C du virus Nipah(2018), ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
Rok vydání: 2021
Předmět:
Zdroj: Journal of Molecular Biology
Journal of Molecular Biology, 2022, 434 (10), pp.167551. ⟨10.1016/j.jmb.2022.167551⟩
ISSN: 1089-8638
0022-2836
Popis: International audience; To understand the dynamic interactions between the phosphoprotein (P) and the nucleoprotein (N) within the transcription/replication complex of the $Paramyxoviridae$ and to decipher their roles in regulating viral multiplication, we characterized the structural properties of the C-terminal X domain (P$_{XD}$) of Nipah (NiV) and Hendra virus (HeV) P protein. In crystals, isolated NiV P$_{XD}$ adopted a two-helix dimeric conformation, which was incompetent for binding its partners, but in complex with the C-terminal intrinsically disordered tail of the N protein (NTAIL), it folded into a canonical 3H bundle conformation. In solution, SEC-MALLS, SAXS and NMR spectroscopy experiments indicated that both NiV and HeV P$_{XD}$ were larger in size than expected for compact proteins of the same molecular mass and were in conformational exchange between a compact three-helix (3H) bundle and partially unfolded conformations, where helix $\alpha_3$ is detached from the other two. Some measurements also provided strong evidence for dimerization of NiV P$_{XD}$ in solution but not for HeV P$_{XD}$. Ensemble modeling of experimental SAXS data and statistical-dynamical modeling reconciled all these data, yielding a model where NiV and HeV P$_{XD}$ exchanged between different conformations, and where NiV but not HeV P$_{XD}$ formed dimers. Finally, recombinant NiV comprising a chimeric P carrying HeV P$_{XD}$ was rescued and compared with parental NiV. Experiments carried out in cellula demonstrated that the replacement of P$_{XD}$ did not significantly affect the replication dynamics while caused a slight virus attenuation, suggesting a possible role of the dimerization of NiV P$_{XD}$ in viral replication.
Databáze: OpenAIRE
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