5IBV

Crystal Structure of Human Astrovirus capsid protein

5IBV の概要

• エントリーDOI: 10.2210/pdb5ibv/pdb
• 分子名称: Capsid polyprotein VP90 (2 entities in total)
• 機能のキーワード: astrovirus, capsid, viral protein
• 由来する生物種: Human astrovirus-8 (HAstV-8)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 37772.75

構造登録者

Tao, Y.J.,Toh, Y.S. (登録日: 2016-02-22, 公開日: 2016-08-03, 最終更新日: 2024-11-20)

主引用文献

Toh, Y.,Harper, J.,Dryden, K.A.,Yeager, M.,Arias, C.F.,Mendez, E.,Tao, Y.J.
Crystal Structure of the Human Astrovirus Capsid Protein.
J.Virol., 90:9008-9017, 2016

PubMed Abstract: Human astrovirus (HAstV) is a leading cause of viral diarrhea in infants and young children worldwide. HAstV is a nonenveloped virus with a T=3 capsid and a positive-sense RNA genome. The capsid protein (CP) of HAstV is synthesized as a 90-kDa precursor (VP90) that can be divided into three linear domains: a conserved N-terminal domain, a hypervariable domain, and an acidic C-terminal domain. Maturation of HAstV requires proteolytic processing of the astrovirus CP both inside and outside the host cell, resulting in the removal of the C-terminal domain and the breakdown of the rest of the CP into three predominant protein species with molecular masses of ∼34, 27/29, and 25/26 kDa, respectively. We have now solved the crystal structure of VP90(71-415) (amino acids [aa] 71 to 415 of VP90) of human astrovirus serotype 8 at a 2.15-Å resolution. VP90(71-415) encompasses the conserved N-terminal domain of VP90 but lacks the hypervariable domain, which forms the capsid surface spikes. The structure of VP90(71-415) is comprised of two domains: an S domain, which adopts the typical jelly-roll β-barrel fold, and a P1 domain, which forms a squashed β-barrel consisting of six antiparallel β-strands similar to what was observed in the hepatitis E virus (HEV) capsid structure. Fitting of the VP90(71-415) structure into the cryo-electron microscopy (EM) maps of HAstV produced an atomic model for a continuous, T=3 icosahedral capsid shell. Our pseudoatomic model of the human HAstV capsid shell provides valuable insights into intermolecular interactions required for capsid assembly and trypsin-mediated proteolytic maturation needed for virus infectivity. Such information has potential applications in the development of a virus-like particle (VLP) vaccine as well as small-molecule drugs targeting astrovirus assembly/maturation.

PubMed: 27466429
DOI: 10.1128/JVI.00694-16

実験手法

X-RAY DIFFRACTION (2.15 Å)