Structure of a rabies virus polymerase complex from electron cryo-microscopy
Abstract
Rabies virus (RABV) and other viruses with single-segment, negative-sense, RNA genomes have a multi-functional polymerase protein (L) that carries out the various reactions required for transcription and replication. Many of these viruses are serious human pathogens, and L is a potential target for antiviral therapeutics. Drugs that inhibit polymerases of HCV and HIV-1 provide successful precedents. The structure described here of the RABV L protein in complex with its P-protein cofactor shows a conformation poised for initiation of transcription or replication. Channels in the molecule and the relative positions of catalytic sites suggest that L couples a distinctive capping reaction with priming and initiation of transcription, and that replication and transcription have different priming configurations and different product exit sites.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- January 2020
- DOI:
- 10.1073/pnas.1918809117
- Bibcode:
- 2020PNAS..117.2099H