4NHH

Structure of 2G12 IgG Dimer

4NHH の概要

• エントリーDOI: 10.2210/pdb4nhh/pdb
• 分子名称: 2G12 IgG dimer light chain, Hepatitis B virus receptor binding protein, 2G12 IgG dimer heavy chain (3 entities in total)
• 機能のキーワード: ig, antibody, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 18
• 化学式量合計: 428576.66

構造登録者

Wu, Y.,West Jr., A.P.,Kim, H.J.,Thornton, M.E.,Ward, A.B.,Bjorkman, P.J. (登録日: 2013-11-05, 公開日: 2014-02-26, 最終更新日: 2024-11-27)

主引用文献

Wu, Y.,West, A.P.,Kim, H.J.,Thornton, M.E.,Ward, A.B.,Bjorkman, P.J.
Structural basis for enhanced HIV-1 neutralization by a dimeric immunoglobulin G form of the glycan-recognizing antibody 2G12.
Cell Rep, 5:1443-1455, 2013

PubMed Abstract: The human immunoglobulin G (IgG) 2G12 recognizes high-mannose carbohydrates on the HIV type 1 (HIV-1) envelope glycoprotein gp120. Its two antigen-binding fragments (Fabs) are intramolecularly domain exchanged, resulting in a rigid (Fab)2 unit including a third antigen-binding interface not found in antibodies with flexible Fab arms. We determined crystal structures of dimeric 2G12 IgG created by intermolecular domain exchange, which exhibits increased breadth and >50-fold increased neutralization potency compared with monomeric 2G12. The four Fab and two fragment crystalline (Fc) regions of dimeric 2G12 were localized at low resolution in two independent structures, revealing IgG dimers with two (Fab)2 arms analogous to the Fabs of conventional monomeric IgGs. Structures revealed three conformationally distinct dimers, demonstrating flexibility of the (Fab)2-Fc connections that was confirmed by electron microscopy, small-angle X-ray scattering, and binding studies. We conclude that intermolecular domain exchange, flexibility, and bivalent binding to allow avidity effects are responsible for the increased potency and breadth of dimeric 2G12.

PubMed: 24316082
DOI: 10.1016/j.celrep.2013.11.015

実験手法

X-RAY DIFFRACTION (6.5 Å)