Structure of a rabies virus polymerase complex from electron cryo-microscopy

Joshua A. Horwitz, Simon Jenni, Stephen C. Harrison, Sean P.J. Whelan

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Nonsegmented negative-stranded (NNS) RNA viruses, among them the virus that causes rabies (RABV), include many deadly human pathogens. The large polymerase (L) proteins of NNS RNA viruses carry all of the enzymatic functions required for viral messenger RNA (mRNA) transcription and replication: RNA polymerization, mRNA capping, and cap methylation. We describe here a complete structure of RABV L bound with its phosphoprotein cofactor (P), determined by electron cryo-microscopy at 3.3 Å resolution. The complex closely resembles the vesicular stomatitis virus (VSV) L-P, the one other known full-length NNS-RNA L-protein structure, with key local differences (e.g., in L-P interactions). Like the VSV L-P structure, the RABV complex analyzed here represents a preinitiation conformation. Comparison with the likely elongation state, seen in two structures of pneumovirus L-P complexes, suggests differences between priming/initiation and elongation complexes. Analysis of internal cavities within RABV L suggests distinct template and product entry and exit pathways during transcription and replication.

Original languageEnglish
Pages (from-to)2099-2107
Number of pages9
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number4
DOIs
StatePublished - Jan 28 2020

Keywords

  • NNS RNA viruses
  • Rabies lyssavirus
  • Replication
  • Transcription
  • Vesicular stomatitis virus

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