3U7W

Crystal structure of NIH45-46 Fab

3U7W の概要

• エントリーDOI: 10.2210/pdb3u7w/pdb
• 関連するPDBエントリー: 3U7Y
• 分子名称: Heavy chain, Ig gamma-1 chain C region, Light chain, Ig kappa chain C region, GLYCEROL, ... (6 entities in total)
• 機能のキーワード: ig fold, antibody, hiv gp120, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48683.33

構造登録者

Diskin, R.,Bjorkman, P.J. (登録日: 2011-10-14, 公開日: 2011-11-16, 最終更新日: 2024-11-20)

主引用文献

Diskin, R.,Scheid, J.F.,Marcovecchio, P.M.,West, A.P.,Klein, F.,Gao, H.,Gnanapragasam, P.N.,Abadir, A.,Seaman, M.S.,Nussenzweig, M.C.,Bjorkman, P.J.
Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design.
Science, 334:1289-1293, 2011

PubMed Abstract: Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01-gp120 revealed that a four-residue insertion in heavy chain complementarity-determining region 3 (CDRH3) contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46(G54W), a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46-gp120 structure, these results indicate that gp120 inner domain and bridging sheet residues should be included in immunogens to elicit CD4bs antibodies.

PubMed: 22033520
DOI: 10.1126/science.1213782

実験手法

X-RAY DIFFRACTION (2.6 Å)