3V7A

Structural basis for broad detection of genogroup II noroviruses by a monoclonal antibody that binds to a site occluded in the viral particle

3V7A の概要

• エントリーDOI: 10.2210/pdb3v7a/pdb
• 関連するPDBエントリー: 3ONU
• 分子名称: 5B18 heavy chain, 5B18 kappa chain, Capsid (3 entities in total)
• 機能のキーワード: virus, protein-fab complex, broadly-reactive antibody, immune system
• 由来する生物種: Human calicivirus; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 163976.75

構造登録者

Hansman, G.S.,Mclellan, J.S.,Kwong, P.D. (登録日: 2011-12-20, 公開日: 2012-02-08, 最終更新日: 2024-11-27)

主引用文献

Hansman, G.S.,Taylor, D.W.,McLellan, J.S.,Smith, T.J.,Georgiev, I.,Tame, J.R.,Park, S.Y.,Yamazaki, M.,Gondaira, F.,Miki, M.,Katayama, K.,Murata, K.,Kwong, P.D.
Structural Basis for Broad Detection of Genogroup II Noroviruses by a Monoclonal Antibody That Binds to a Site Occluded in the Viral Particle.
J.Virol., 86:3635-3646, 2012

PubMed Abstract: Human noroviruses are genetically and antigenically highly divergent. Monoclonal antibodies raised in mice against one kind of norovirus virus-like particle (VLP), however, were found to have broad recognition. In this study, we present the crystal structure of the antigen-binding fragment (Fab) for one of these broadly reactive monoclonal antibodies, 5B18, in complex with the capsid-protruding domain from a genogroup II genotype 10 (GII.10) norovirus at 3.3-Å resolution and, also, the cryo-electron microscopy structure of the GII.10 VLP at ∼10-Å resolution. The GII.10 VLP structure was more similar in overall architecture to the GV.1 murine norovirus virion than to the prototype GI.1 human norovirus VLP, with the GII.10 protruding domain raised ∼15 Å off the shell domain and rotated ∼40° relative to the GI.1 protruding domain. In the crystal structure, the 5B18 Fab bound to a highly conserved region of the protruding domain. Based on the VLP structure, this region is involved in interactions with other regions of the capsid and is buried in the virus particle. Despite the occluded nature of the recognized epitope in the VLP structure, enzyme-linked immunosorbent assay (ELISA) binding suggested that the 5B18 antibody was able to capture intact VLPs. Together, the results provide evidence that the norovirus particle is capable of extreme conformational flexibility, which may allow for antibody recognition of conserved surfaces that would otherwise be buried on intact particles.

PubMed: 22278249
DOI: 10.1128/JVI.06868-11

実験手法

X-RAY DIFFRACTION (3.297 Å)