Cell
Volume 162, Issue 2, 16 July 2015, Pages 314-327
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Article
Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy

https://doi.org/10.1016/j.cell.2015.06.018Get rights and content
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Highlights

  • Vesicular stomatitis virus L protein structure from cryo-EM at 3.8 Å resolution

  • Full de novo chain trace: RdRp, capping, MTase, and two structural domains

  • P protein locks L in an initiation competent state with all five domains fixed

  • Homology with other NNS virus polymerases (e.g., Ebola virus, RSV)

Summary

The large (L) proteins of non-segmented, negative-strand RNA viruses, a group that includes Ebola and rabies viruses, catalyze RNA-dependent RNA polymerization with viral ribonucleoprotein as template, a non-canonical sequence of capping and methylation reactions, and polyadenylation of viral messages. We have determined by electron cryomicroscopy the structure of the vesicular stomatitis virus (VSV) L protein. The density map, at a resolution of 3.8 Å, has led to an atomic model for nearly all of the 2109-residue polypeptide chain, which comprises three enzymatic domains (RNA-dependent RNA polymerase [RdRp], polyribonucleotidyl transferase [PRNTase], and methyltransferase) and two structural domains. The RdRp resembles the corresponding enzymatic regions of dsRNA virus polymerases and influenza virus polymerase. A loop from the PRNTase (capping) domain projects into the catalytic site of the RdRp, where it appears to have the role of a priming loop and to couple product elongation to large-scale conformational changes in L.

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