Ensemble Structure of the Modular and Flexible Full-Length Vesicular Stomatitis Virus Phosphoprotein

• Published in: Journal of molecular biology Vol. 423; no. 2; pp. 182 - 197
• Main Authors: Leyrat, Cédric, Schneider, Robert, Ribeiro, Euripedes A., Yabukarski, Filip, Yao, Mingxi, Gérard, Francine C.A., Jensen, Malene Ringkjøbing, Ruigrok, Rob W.H., Blackledge, Martin, Jamin, Marc
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 19.10.2012
• Subjects: intrinsically disordered regions; Models, Molecular; NMR; Nuclear Magnetic Resonance, Biomolecular; phosphoprotein; Phosphoproteins - chemistry; Phosphoproteins - metabolism; Protein Conformation; RNA, Viral - chemistry; RNA, Viral - metabolism; SAXS; Vesicular stomatitis Indiana virus - metabolism; Vesicular stomatitis virus; Viral Structural Proteins - chemistry; Viral Structural Proteins - metabolism; Virus Replication; SEC; SSP; NMR; phosphoprotein; IDR; vesicular stomatitis virus; VSV; HSQC; SAXS; intrinsically disordered regions
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2012.07.003

The phosphoprotein (P) is an essential component of the viral replication machinery of non-segmented negative‐strand RNA viruses, connecting the viral polymerase to its nucleoprotein–RNA template and acting as a chaperone of the nucleoprotein by preventing nonspecific encapsidation of cellular RNAs. The phosphoprotein of vesicular stomatitis virus (VSV) forms homodimers and possesses a modular organization comprising two stable, well-structured domains concatenated with two intrinsically disordered regions. Here, we used a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering to depict VSV P as an ensemble of continuously exchanging conformers that captures the dynamic character of this protein. We discuss the implications of the dynamics and the large conformational space sampled by VSV P in the assembly and functioning of the viral transcription/replication machinery. [Display omitted] ► Combined nuclear magnetic resonance and small‐angle X‐ray scattering approaches to characterize the structure of VSV phosphoprotein. ► The structure is described as a conformational ensemble. ► Roles are proposed for the flexibility of VSV phosphoprotein. ► New insights about the structural organization of the replication complex are gained.