5ACA

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

5ACA の概要

• エントリーDOI: 10.2210/pdb5aca/pdb
• 関連するPDBエントリー: 5AC9
• EMDBエントリー: 3130
• 分子名称: VP1, VP2, VP3, ... (4 entities in total)
• 機能のキーワード: virus, vaccine, foot and mouth disease virus, fmdv
• 由来する生物種: FOOT-AND-MOUTH DISEASE VIRUS - TYPE SAT 2; 詳細
• 細胞内の位置: Virion : Q1L764 Q1L764 Q1L764 Q1L764
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80842.79

構造登録者

Kotecha, A.,Seago, J.,Scott, K.,Burman, A.,Loureiro, S.,Ren, J.,Porta, C.,Ginn, H.M.,Jackson, T.,Perez-Martin, E.,Siebert, C.A.,Paul, G.,Huiskonen, J.T.,Jones, I.M.,Esnouf, R.M.,Fry, E.E.,Maree, F.F.,Charleston, B.,Stuart, D.I. (登録日: 2015-08-14, 公開日: 2015-09-23, 最終更新日: 2024-05-08)

主引用文献

Kotecha, A.,Seago, J.,Scott, K.,Burman, A.,Loureiro, S.,Ren, J.,Porta, C.,Ginn, H.M.,Jackson, T.,Perez-Martin, E.,Siebert, C.A.,Paul, G.,Huiskonen, J.T.,Jones, I.M.,Esnouf, R.M.,Fry, E.E.,Maree, F.F.,Charleston, B.,Stuart, D.I.
Structure-Based Energetics of Protein Interfaces Guide Foot-and-Mouth Disease Vaccine Design
Nat.Struct.Mol.Biol., 22:788-, 2015

PubMed Abstract: 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.

PubMed: 26389739
DOI: 10.1038/NSMB.3096

実験手法

ELECTRON MICROSCOPY (3.5 Å)