Structure of the Respiratory Syncytial Virus Polymerase Complex - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Article Dans Une Revue Cell Année : 2019

Structure of the Respiratory Syncytial Virus Polymerase Complex

Résumé

Numerous interventions are in clinical development for respiratory syncytial virus (RSV) infection, including small molecules that target viral transcrip- tion and replication. These processes are catalyzed by a complex comprising the RNA-dependent RNA polymerase (L) and the tetrameric phosphoprotein (P). RSV P recruits multiple proteins to the polymer- ase complex and, with the exception of its oligomer- ization domain, is thought to be intrinsically disordered. Despite their critical roles in RSV tran- scription and replication, structures of L and P have remained elusive. Here, we describe the 3.2-A˚ cryo- EM structure of RSV L bound to tetrameric P. The structure reveals a striking tentacular arrangement of P, with each of the four monomers adopting a distinct conformation. The structure also rationalizes inhibitor escape mutants and mutations observed in live-attenuated vaccine candidates. These results provide a framework for determining the molecular underpinnings of RSV replication and transcription and should facilitate the design of effective RSV inhibitors
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hal-04671067 , version 1 (13-08-2024)

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Morgan S.A. Gilman, Cheng Liu, Amy Fung, Ishani Behera, Paul Jordan, et al.. Structure of the Respiratory Syncytial Virus Polymerase Complex. Cell, 2019, 179 (1), pp.193-204.e14. ⟨10.1016/j.cell.2019.08.014⟩. ⟨hal-04671067⟩
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