Structural highlights
Publication Abstract from PubMed
Viral RNA-dependent RNA polymerases (RdRPs) play central roles in the genome replication and transcription processes of RNA viruses. RdRPs initiate RNA synthesis either in primer-dependent or de novo mechanism, with the latter often assisted by a 'priming element' (PE) within the RdRP thumb domain. However, RdRP PEs exhibit high-level structural diversity, making it difficult to reconcile their conserved function in de novo initiation. Here we determined a 3.1-A crystal structure of the Flaviviridae classical swine fever virus (CSFV) RdRP with a relative complete PE. Structure-based mutagenesis in combination with enzymology data further highlights the importance of a glycine residue (G671) and the participation of residues 665-680 in RdRP initiation. When compared with other representative Flaviviridae RdRPs, CSFV RdRP PE is structurally distinct but consistent in terminal initiation preference. Taken together, our work suggests that a conformational change in CSFV RdRP PE is necessary to fulfill de novo initiation, and similar 'induced-fit' mechanisms may be commonly taken by PE-containing de novo viral RdRPs.
An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase.,Zhang BY, Liu W, Jia H, Lu G, Gong P Nucleic Acids Res. 2021 Sep 7;49(15):8811-8821. doi: 10.1093/nar/gkab666. PMID:34365500[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang BY, Liu W, Jia H, Lu G, Gong P. An induced-fit de novo initiation mechanism suggested by a pestivirus RNA-dependent RNA polymerase. Nucleic Acids Res. 2021 Sep 7;49(15):8811-8821. doi: 10.1093/nar/gkab666. PMID:34365500 doi:http://dx.doi.org/10.1093/nar/gkab666
