3TNM

Crystal structure of A32 Fab, an ADCC mediating anti-HIV-1 antibody

3TNM の概要

• エントリーDOI: 10.2210/pdb3tnm/pdb
• 関連するPDBエントリー: 3QEG 3QEH 3TNN
• 分子名称: Fab heavy chain of human anti-HIV-1 Env antibody A32, Fab light chain of human anti-HIV-1 Env antibody A32, ACETATE ION, ... (5 entities in total)
• 機能のキーワード: adcc, non-neutralizing, anti-hiv-1 env antibody a32, cd4i antibody, fab, viral glycoprotein gp120, hiv-1 env, 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: 95356.96

構造登録者

Wu, X.,Pazgier, M. (登録日: 2011-09-01, 公開日: 2012-09-26, 最終更新日: 2024-11-20)

主引用文献

Guan, Y.,Pazgier, M.,Sajadi, M.M.,Kamin-Lewis, R.,Al-Darmarki, S.,Flinko, R.,Lovo, E.,Wu, X.,Robinson, J.E.,Seaman, M.S.,Fouts, T.R.,Gallo, R.C.,DeVico, A.L.,Lewis, G.K.
Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding.
Proc.Natl.Acad.Sci.USA, 110:E69-E78, 2013

PubMed Abstract: The HIV-1 envelope glycoprotein (Env) undergoes conformational transitions consequent to CD4 binding and coreceptor engagement during viral entry. The physical steps in this process are becoming defined, but less is known about their significance as targets of antibodies potentially protective against HIV-1 infection. Here we probe the functional significance of transitional epitope exposure by characterizing 41 human mAbs specific for epitopes exposed on trimeric Env after CD4 engagement. These mAbs recognize three epitope clusters: cluster A, the gp120 face occluded by gp41 in trimeric Env; cluster B, a region proximal to the coreceptor-binding site (CoRBS) and involving the V1/V2 domain; and cluster C, the coreceptor-binding site. The mAbs were evaluated functionally by antibody-dependent, cell-mediated cytotoxicity (ADCC) and for neutralization of Tiers 1 and 2 pseudoviruses. All three clusters included mAbs mediating ADCC. However, there was a strong potency bias for cluster A, which harbors at least three potent ADCC epitopes whose cognate mAbs have electropositive paratopes. Cluster A epitopes are functional ADCC targets during viral entry in an assay format using virion-sensitized target cells. In contrast, only cluster C contained epitopes that were recognized by neutralizing mAbs. There was significant diversity in breadth and potency that correlated with epitope fine specificity. In contrast, ADCC potency had no relationship with neutralization potency or breadth for any epitope cluster. Thus, Fc-mediated effector function and neutralization coselect with specificity in anti-Env antibody responses, but the nature of selection is distinct for these two antiviral activities.

PubMed: 23237851
DOI: 10.1073/pnas.1217609110

実験手法

X-RAY DIFFRACTION (1.85 Å)