RT Journal Article
SR Electronic
T1 Structure of a rabies virus polymerase complex from electron cryo-microscopy
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 794073
DO 10.1101/794073
A1 Joshua A. Horwitz
A1 Simon Jenni
A1 Stephen C. Harrison
A1 Sean P.J. Whelan
YR 2019
UL http://biorxiv.org/content/early/2019/10/06/794073.abstract
AB Non-segmented 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 the enzymatic functions required for viral mRNA transcription and replication: RNA polymerization, mRNA capping, 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 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 pre-initiation conformation. Comparison with the likely elongation state, seen in two partial 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.