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-Structure paper
タイトル | Structure-based energetics of protein interfaces guides foot-and-mouth disease virus vaccine design. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 22, Issue 10, Page 788-794, Year 2015 |
掲載日 | 2015年9月21日 |
著者 | Abhay Kotecha / Julian Seago / Katherine Scott / Alison Burman / Silvia Loureiro / Jingshan Ren / Claudine Porta / Helen M Ginn / Terry Jackson / Eva Perez-Martin / C Alistair Siebert / Guntram Paul / Juha T Huiskonen / Ian M Jones / Robert M Esnouf / Elizabeth E Fry / Francois F Maree / Bryan Charleston / David I Stuart / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:26389739 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.4 - 3.5 Å |
構造データ | EMDB-3129: Structure-based energetics of protein interfaces guide FMDV vaccine design EMDB-3130: Structure-based energetics of protein interfaces guide FMDV vaccine design PDB-5d8a: PDB-5ddj: |
化合物 | ChemComp-HOH: |
由来 |
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キーワード | VIRUS / VACCINE / FOOT AND MOUTH DISEASE VIRUS / FMDV / picornavirus / aphthovirus |