5ac9

Structure-based energetics of protein interfaces guide Foot-and-Mouth disease virus vaccine design

Loading... Status: waiting for Mol* initialization Structural highlights 5ac9 is a 4 chain structure with sequence from Foot-and-mouth disease virus O. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6PMW3_9PICO Publication Abstract from PubMed Virus capsids are primed for disassembly, yet capsid integrity is key to generating a protective immune response. Foot-and-mouth disease virus (FMDV) capsids comprise identical pentameric protein subunits held together by tenuous noncovalent interactions and are often unstable. Chemically inactivated or recombinant empty capsids, which could form the basis of future vaccines, are even less stable than live virus. Here we devised a computational method to assess the relative stability of protein-protein interfaces and used it to design improved candidate vaccines for two poorly stable, but globally important, serotypes of FMDV: O and SAT2. We used a restrained molecular dynamics strategy to rank mutations predicted to strengthen the pentamer interfaces and applied the results to produce stabilized capsids. Structural analyses and stability assays confirmed the predictions, and vaccinated animals generated improved neutralizing-antibody responses to stabilized particles compared to parental viruses and wild-type capsids. Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design.,Kotecha A, Seago J, Scott K, Burman A, Loureiro S, Ren J, Porta C, Ginn HM, Jackson T, Perez-Martin E, Siebert CA, Paul G, Huiskonen JT, Jones IM, Esnouf RM, Fry EE, Maree FF, Charleston B, Stuart DI Nat Struct Mol Biol. 2015 Sep 21. doi: 10.1038/nsmb.3096. PMID:26389739 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Virus coat proteins 3D structures

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