2m4h | pdb_00002m4h
Solution structure of the Core Domain (10-76) of the Feline Calicivirus VPg protein
Structural highlights
Function[POLG_FCVF9] NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity (By similarity). Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation (By similarity). Protease-polymerase p76 processes the polyprotein: Pro-Pol is first released by autocleavage, then all other proteins are cleaved. Cleaves host translation initiation factor eIF4G1 and eIF4G2 thereby inducing a shutdown of host protein synthesis. This shutdown may not prevent viral mRNA from being translated since viral Vpg replaces the cap. May cleave host polyadenylate-binding protein thereby inhibiting cellular translation. It is also a RNA-directed RNA polymerase which replicates genomic and antigenomic viral RNA by recognizing specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA encodes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity). Publication Abstract from PubMedWe report the solution structures of the VPg proteins from feline calicivirus (FCV) and murine norovirus (MNV), which have been determined by nuclear magnetic resonance spectroscopy. In both cases the core of the protein adopts a compact helical structure flanked by flexible N and C-termini. Remarkably, while the core of FCV VPg contains a well-defined three-helix bundle, the MNV VPg core has just the first two of these secondary structure elements. In both cases the VPg cores are stabilised by networks of hydrophobic and salt-bridge interactions. The Tyr residue in VPg that is nucleotidylated by the viral NS7 polymerase (Y24 in FCV, Y26 in MNV) occurs in a conserved position within the first helix of the core. Intriguingly, given its structure, VPg would appear to be unable to bind to the viral polymerase so as to place this Tyr in the active site without a major conformation change to VPg or the polymerase. However, mutations that destabilised the VPg core either had no effect on or reduced both the ability of the protein to be nucleotidylated and virus infectivity and did not reveal a clear structure-activity relationship. The precise role of the calicivirus VPg core in virus replication remains to be determined but knowledge of its structure will facilitate future investigations. Structures of the Compact Helical Core Domains of Feline Calicivirus and Murine Norovirus VPg proteins.,Leen EN, Kwok KY, Birtley JR, Simpson PJ, Subba-Reddy CV, Chaudhry Y, Sosnovtsev SV, Green KY, Prater SN, Young JC, Chung LM, Marchant J, Roberts LO, Kao CC, Matthews S, Goodfellow IG, Curry S J Virol. 2013 Mar 13. PMID:23487472[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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