5aca

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

5aca, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Structural highlights 5aca is a 4 chain structure with sequence from Foot-and-mouth disease virus SAT 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q719N0_9PICO Associates with and induces structural rearrangements of intracellular membranes. Triggers host autophagy by interacting with host BECN1 and thereby promotes viral replication. Participates in viral replication and interacts with host DHX9. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3.[ARBA:ARBA00003578] Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome-linked replication primer.[ARBA:ARBA00002573] Cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, binds to viral RNA and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease.[ARBA:ARBA00004047] Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome.[ARBA:ARBA00033732] Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3. The capsid is composed of 60 copies of each capsid protein organized in the form of twelve pentamers and encloses the viral positive strand RNA genome.[ARBA:ARBA00033735] Lies on the inner surface of the capsid shell. After binding to the host receptor, the capsid undergoes conformational changes. Capsid protein VP4 is released, capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm. After genome has been released, the channel shrinks.[ARBA:ARBA00033716] Mediates self-processing of the polyprotein by a translational effect termed 'ribosome skipping'. Mechanistically, 2A-mediated cleavage occurs between the C-terminal glycine and the proline of the downstream protein 2B. In the case of foot-and-mouth disease virus, the 2A oligopeptide is post-translationally 'trimmed' from the C-terminus of the upstream protein 1D by 3C proteinase.[ARBA:ARBA00002616] Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication.[ARBA:ARBA00003379] RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated.[ARBA:ARBA00004027] 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