ABSTRACT
X-ray structures, at almost atomic resolution, of Foot-and-Mouth-Disease Virus (FMDV) particles from several serotypes and subtypes are now available mainly from the results obtained by the Oxford group during about the last 15 years. FMDVs show many of the structural features generally found in picornaviruses with virions forming icosahedral shells composed of 60 copies each of four structural proteins VP1-VP4. The disposition of the three larger proteins, VP1-VP3, follows a pseudo T=3 architecture (P=3) closely related to the one first found in small, RNA, plant viruses. The arrangement is possible because of the similar topology of VP1, VP2 and VP3, which adopt the wedge-shaped eight-stranded -barrel fold characteristic of most RNA viruses. The chain length and conformation of VP4 is quite variable among picornaviruses, though the protein is always internal and has an N-terminal myristoyl group that in the FMDV structures remains undefined. Despite the important features in common with picornaviruses, FMDV presents some major differences that can often be related to functional or biological peculiarities. In particular, the canyon or pit found in most picornaviruses is absent in aphthoviruses, which place the integrin cell attachment site containing the Arg-Gly-Asp (RGD) motif in the protruding, fully exposed and highly immunogenic GH loop from VP1, also called the “FMDV loop”. Some flexibility seems required for the optimal biological functionality of this loop that has always been found disordered in the crystal structures of the unperturbed virions. However, the structure of the loop has been trapped, both in crystals of reduced virions from the O serotype, and in crystals of peptide complexes with neutralizing antibodies against the C serotype. The self-contained structure of the “FMDV loop” together with its hinge flexibility and with the recent availability of the structure of the ectodomain from integrin αvβ3 suggest mechanisms for cell receptor-virus recognition and specificity.
