Structural highlights
Function
[POLG_FMDV1] The leader protease autocatalytically cleaves itself from the polyprotein at the L/VP0 junction. It cleaves the host translation initiation factors EIF4G1 and EIF4G3, in order to shut down the capped cellular mRNA transcription (By similarity). Capsid proteins VP1, VP2, VP3 and VP4 form a closed capsid enclosing the viral positive strand RNA genome. VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll. Together they form an icosahedral capsid (T=3) composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. The capsid interacts with host heparan sulfate and various integrins (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8) to provide virion attachment to target Attachment via host integrins induces virion internalization predominantly through clathrin-mediated endocytosis (By similarity). Protein VP0: VP0 precursor is a component of immature procapsids (By similarity). Protein 2B: Affects membrane integrity and cause an increase in membrane permeability (By similarity). Protein 2C: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Protein 3A, via its hydrophobic domain, serves as membrane anchor (By similarity). Protein 3B-1, 3B-2 and 3B-3 are covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. They acts as a genome-linked replication primer (By similarity). Protease 3C: cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Foot-and-mouth disease viruses (FMDVs) target epithelial cells via integrin receptors, but can acquire the capacity to bind cell-surface heparan sulphate (or alternative receptors) on passage in cell culture. Vaccine viruses must be propagated in cell culture and, hence, some rationale for the selection of variants in this process is important. Crystal structures are available for type O, A and C viruses and also for a complex of type O strain O(1)BFS with heparin. The structure of FMDV A10(61) (a cell culture-adapted strain) complexed with heparin has now been determined. This virus has an RGSD motif in place of the otherwise conserved RGD integrin-binding motif and the potential to bind heparan sulphate (suggested by sequence analyses). FMDV A10(61) was closely similar in structure to other serotypes, deviating most in antigenic sites. The VP1 GH loop comprising the integrin-binding motif was disordered. Heparin bound at a similar site and in a similar conformation to that seen in the analogous complex with O(1)BFS, although the binding had a lower affinity and was more ionic.
Structure of Foot-and-mouth disease virus serotype A10 61 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation.,Fry EE, Newman JW, Curry S, Najjam S, Jackson T, Blakemore W, Lea SM, Miller L, Burman A, King AM, Stuart DI J Gen Virol. 2005 Jul;86(Pt 7):1909-20. PMID:15958669[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Fry EE, Newman JW, Curry S, Najjam S, Jackson T, Blakemore W, Lea SM, Miller L, Burman A, King AM, Stuart DI. Structure of Foot-and-mouth disease virus serotype A10 61 alone and complexed with oligosaccharide receptor: receptor conservation in the face of antigenic variation. J Gen Virol. 2005 Jul;86(Pt 7):1909-20. PMID:15958669 doi:86/7/1909
