Structural highlights
Function
G4W9T5_9PICO Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome.[ARBA:ARBA00002133] Affects membrane integrity and causes an increase in membrane permeability.[ARBA:ARBA00004017] Plays a role in the assembly of the 12 pentamers into an icosahedral structure. Has not been detected in mature virions, supposedly owing to its small size.[ARBA:ARBA00002016] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals.[ARBA:ARBA00003097] VP0 precursor is a component of the immature procapsids.[ARBA:ARBA00003724]
Publication Abstract from PubMed
The HAV nonstructural protein 2C is essential for virus replication; however, its precise function remains elusive. Although HAV 2C shares 24-27% sequence identity with other 2Cs, key motifs are conserved. Here, we demonstrate that HAV 2C is an ATPase but lacking helicase activity. We identified an ATPase-independent nuclease activity of HAV 2C with a preference for polyuridylic single-stranded RNAs. We determined the crystal structure of an HAV 2C fragment to 2.2 A resolution, containing an ATPase domain, a region equivalent to enterovirus 2C zinc-finger (ZFER) and a C-terminal amphipathic helix (PBD). The PBD of HAV 2C occupies a hydrophobic pocket (Pocket) in the adjacent 2C, and we show the PBD-Pocket interaction is vital for 2C functions. We identified acidic residues that are essential for the ribonuclease activity and demonstrated mutations at these sites abrogate virus replication. We built a hexameric-ring model of HAV 2C, revealing the ribonuclease-essential residues clustering around the central pore of the ring, whereas the ATPase active sites line up at the gaps between adjacent 2Cs. Finally, we show the ribonuclease activity is shared by other picornavirus 2Cs. Our findings identified a previously unfound activity of picornavirus 2C, providing novel insights into the mechanisms of virus replication.
Biochemical and structural characterization of hepatitis A virus 2C reveals an unusual ribonuclease activity on single-stranded RNA.,Chen P, Wojdyla JA, Colasanti O, Li Z, Qin B, Wang M, Lohmann V, Cui S Nucleic Acids Res. 2022 Aug 10. pii: 6659853. doi: 10.1093/nar/gkac671. PMID:35947700[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen P, Wojdyla JA, Colasanti O, Li Z, Qin B, Wang M, Lohmann V, Cui S. Biochemical and structural characterization of hepatitis A virus 2C reveals an unusual ribonuclease activity on single-stranded RNA. Nucleic Acids Res. 2022 Aug 10. pii: 6659853. doi: 10.1093/nar/gkac671. PMID:35947700 doi:https://dx.doi.org/10.1093/nar/gkac671
