4EBQ

Fab structure of anti-Vaccinia virus D8L antigen mouse IgG2a LA5

4EBQ の概要

• エントリーDOI: 10.2210/pdb4ebq/pdb
• 関連するPDBエントリー: 2I9L 4E9O
• 分子名称: anti-Vaccinia D8L antigen monoclonal IgG2a antibody LA5, heavy chain, anti-Vaccinia D8L antigen monoclonal IgG2a antibody LA5, light chain, GLYCEROL, ... (7 entities in total)
• 機能のキーワード: variable domain, constant domain, cdr, hypervariable region, neutralizing antibody, vaccinia virus, d8l envelope protein, conformational epitope, discontinuous epitope, d8l antigen binding, neutralizing mab in presence of complement, d8l vaccinia envelope protein, papain treatment, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47699.57

構造登録者

Matho, M.H.,Zajonc, D.M. (登録日: 2012-03-23, 公開日: 2012-06-06, 最終更新日: 2024-11-27)

主引用文献

Matho, M.H.,Maybeno, M.,Benhnia, M.R.,Becker, D.,Meng, X.,Xiang, Y.,Crotty, S.,Peters, B.,Zajonc, D.M.
Structural and Biochemical Characterization of the Vaccinia Virus Envelope Protein D8 and Its Recognition by the Antibody LA5.
J.Virol., 86:8050-8058, 2012

PubMed Abstract: Smallpox vaccine is considered a gold standard of vaccines, as it is the only one that has led to the complete eradication of an infectious disease from the human population. B cell responses are critical for the protective immunity induced by the vaccine, yet their targeted epitopes recognized in humans remain poorly described. Here we describe the biochemical and structural characterization of one of the immunodominant vaccinia virus (VACV) antigens, D8, and its binding to the monoclonal antibody LA5, which is capable of neutralizing VACV in the presence of complement. The full-length D8 ectodomain was found to form a tetramer. We determined the crystal structure of the LA5 Fab-monomeric D8 complex at a resolution of 2.1 Å, as well as the unliganded structures of D8 and LA5-Fab at resolutions of 1.42 Å and 1.6 Å, respectively. D8 features a carbonic anhydrase (CAH) fold that has evolved to bind to the glycosaminoglycan (GAG) chondroitin sulfate (CS) on host cells. The central positively charged crevice of D8 was predicted to be the CS binding site by automated docking experiments. Furthermore, sequence alignment of various poxvirus D8 orthologs revealed that this crevice is structurally conserved. The D8 epitope is formed by 23 discontinuous residues that are spread across 80% of the D8 protein sequence. Interestingly, LA5 binds with a high-affinity lock-and-key mechanism above this crevice with an unusually large antibody-antigen interface, burying 2,434 Å(2) of protein surface.

PubMed: 22623786
DOI: 10.1128/JVI.00836-12

実験手法

X-RAY DIFFRACTION (1.6 Å)