4IV1

Crystal structure of recombinant foot-and-mouth-disease virus A22 empty capsid

4IV1 の概要

• エントリーDOI: 10.2210/pdb4iv1/pdb
• 分子名称: Capsid protein VP1, Capsid protein VP2, Capsid protein VP3, ... (5 entities in total)
• 機能のキーワード: icosahedral virus, capsids, picornavirus, apthovirus, virus, vaccine
• 由来する生物種: Foot-and-mouth disease virus - type A; 詳細
• 細胞内の位置: Picornain 3C: Host cytoplasm (By similarity): Q6PN23 Q6PN23 Q6PN23 Q6PN23
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 80751.24

構造登録者

Porta, C.,Kotecha, A.,Burman, A.,Jackson, T.,Ren, J.,Loureiro, S.,Jones, I.M.,Fry, E.E.,Stuart, D.I.,Charleston, B. (登録日: 2013-01-22, 公開日: 2013-04-17, 最終更新日: 2023-09-20)

主引用文献

Porta, C.,Kotecha, A.,Burman, A.,Jackson, T.,Ren, J.,Loureiro, S.,Jones, I.M.,Fry, E.E.,Stuart, D.I.,Charleston, B.
Rational engineering of recombinant picornavirus capsids to produce safe, protective vaccine antigen.
Plos Pathog., 9:e1003255-e1003255, 2013

PubMed Abstract: Foot-and-mouth disease remains a major plague of livestock and outbreaks are often economically catastrophic. Current inactivated virus vaccines require expensive high containment facilities for their production and maintenance of a cold-chain for their activity. We have addressed both of these major drawbacks. Firstly we have developed methods to efficiently express recombinant empty capsids. Expression constructs aimed at lowering the levels and activity of the viral protease required for the cleavage of the capsid protein precursor were used; this enabled the synthesis of empty A-serotype capsids in eukaryotic cells at levels potentially attractive to industry using both vaccinia virus and baculovirus driven expression. Secondly we have enhanced capsid stability by incorporating a rationally designed mutation, and shown by X-ray crystallography that stabilised and wild-type empty capsids have essentially the same structure as intact virus. Cattle vaccinated with recombinant capsids showed sustained virus neutralisation titres and protection from challenge 34 weeks after immunization. This approach to vaccine antigen production has several potential advantages over current technologies by reducing production costs, eliminating the risk of infectivity and enhancing the temperature stability of the product. Similar strategies that will optimize host cell viability during expression of a foreign toxic gene and/or improve capsid stability could allow the production of safe vaccines for other pathogenic picornaviruses of humans and animals.

PubMed: 23544011
DOI: 10.1371/journal.ppat.1003255

実験手法

X-RAY DIFFRACTION (2.1 Å)