3O2D

Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody

3O2D の概要

• エントリーDOI: 10.2210/pdb3o2d/pdb
• 分子名称: ibalizumab light chain, ibalizumab heavy chain, T-cell surface glycoprotein CD4, ... (4 entities in total)
• 機能のキーワード: immunoglobulin fold, hiv-1 primary receptor, t cell coreceptor, monoclonal antibody, membrane, immune system
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cell membrane; Single-pass type I membrane protein: P01730
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 69577.77

構造登録者

Freeman, M.M.,Seaman, M.S.,Rits-Volloch, S.,Hong, X.,Ho, D.D.,Chen, B. (登録日: 2010-07-22, 公開日: 2010-12-22, 最終更新日: 2024-10-09)

主引用文献

Freeman, M.M.,Seaman, M.S.,Rits-Volloch, S.,Hong, X.,Kao, C.Y.,Ho, D.D.,Chen, B.
Crystal Structure of HIV-1 Primary Receptor CD4 in Complex with a Potent Antiviral Antibody.
Structure, 18:1632-1641, 2010

PubMed Abstract: Ibalizumab is a humanized, anti-CD4 monoclonal antibody. It potently blocks HIV-1 infection and targets an epitope in the second domain of CD4 without interfering with immune functions mediated by interaction of CD4 with major histocompatibility complex (MHC) class II molecules. We report here the crystal structure of ibalizumab Fab fragment in complex with the first two domains (D1-D2) of CD4 at 2.2 Å resolution. Ibalizumab grips CD4 primarily by the BC-loop (residues 121-125) of D2, sitting on the opposite side of gp120 and MHC-II binding sites. No major conformational change in CD4 accompanies binding to ibalizumab. Both monovalent and bivalent forms of ibalizumab effectively block viral infection, suggesting that it does not need to crosslink CD4 to exert antiviral activity. While gp120-induced structural rearrangements in CD4 are probably minimal, CD4 structural rigidity is dispensable for ibalizumab inhibition. These results could guide CD4-based immunogen design and lead to a better understanding of HIV-1 entry.

PubMed: 21134642
DOI: 10.1016/j.str.2010.09.017

実験手法

X-RAY DIFFRACTION (2.19 Å)