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 - Université Grenoble Alpes Accéder directement au contenu
Article Dans Une Revue Journal of Molecular Biology Année : 2022

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

Filip Yabukarski
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Robert Schneider
Francine Gérard
Caroline Mas
Nicolas Tarbouriech
Viktor Volchkov
Martin Blackledge
Marc Jamin

Résumé

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.

Dates et versions

hal-03651805 , version 1 (26-04-2022)

Identifiants

Citer

Jean-Marie Bourhis, Filip Yabukarski, Guillaume Communie, Robert Schneider, Valentina Volchkova, et al.. 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. Journal of Molecular Biology, 2022, 434 (10), pp.167551. ⟨10.1016/j.jmb.2022.167551⟩. ⟨hal-03651805⟩
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