1RHH

Crystal Structure of the Broadly HIV-1 Neutralizing Fab X5 at 1.90 Angstrom Resolution

1RHH の概要

• エントリーDOI: 10.2210/pdb1rhh/pdb
• 関連するPDBエントリー: 1G9M 1G9N 1HZH 3FCT
• 分子名称: Fab X5, light chain, Fab X5, heavy chain (3 entities in total)
• 機能のキーワード: fab, antibody, x5, hiv-1, broadly neutralizing, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97381.93

構造登録者

Darbha, R.,Phogat, S.,Labrijn, A.F.,Shu, Y.,Gu, Y.,Andrykovitch, M.,Zhang, M.Y.,Pantophlet, R.,Martin, L.,Vita, C.,Burton, D.R.,Dimitrov, D.S.,Ji, X. (登録日: 2003-11-14, 公開日: 2004-02-24, 最終更新日: 2024-11-20)

主引用文献

Darbha, R.,Phogat, S.,Labrijn, A.F.,Shu, Y.,Gu, Y.,Andrykovitch, M.,Zhang, M.Y.,Pantophlet, R.,Martin, L.,Vita, C.,Burton, D.R.,Dimitrov, D.S.,Ji, X.
Crystal Structure of the Broadly Cross-Reactive HIV-1-Neutralizing Fab X5 and Fine Mapping of Its Epitope
Biochemistry, 43:1410-1417, 2004

PubMed Abstract: The human monoclonal antibody Fab X5 neutralizes a broad range of HIV-1 primary isolates. The crystal structure of X5 has been determined at 1.9 A resolution. There are two crystallographically independent Fab fragments in the asymmetric unit. The crystallographic R value for the final model is 0.22. The antibody-combining site features a long (22 amino acid residues) CDR H3 with a protruding hook-shaped motif. The X5 structure and site-directed mutagenesis data suggest that X5 amino acid residues W100 and Y100F in the CDR H3 motif may be critical for the binding of Fab X5 to gp120. X5 bound to a complex of a CD4 mimetic and gp120 with approximately the same kinetics and affinity as to a CD4-gp120 complex, suggesting that specific interactions between CD4 and X5 are unlikely to contribute to the binding of X5 to gp120-CD4 complexes. Binding of X5 to alanine scanning mutants of gp120JR-CSF complexed with CD4 suggested a critical role of the highly conserved amino acid residues at positions 423 and 432. The X5 structure and fine mapping of its epitope may assist in the elucidation of the mechanisms of viral entry and neutralization, and the development of HIV-1 inhibitors and vaccines.

PubMed: 14769016
DOI: 10.1021/bi035323x

実験手法

X-RAY DIFFRACTION (1.9 Å)