4TOY

Structure of 35O22 Fab, a HIV-1 neutralizing antibody

4TOY の概要

• エントリーDOI: 10.2210/pdb4toy/pdb
• 分子名称: 35O22 Fab Heavy chain, 35O22 Fab Light chain (3 entities in total)
• 機能のキーワード: hiv-1, antibody, fab, 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: 2
• 化学式量合計: 49472.33

構造登録者

Pancera, M.,Kwong, P.D. (登録日: 2014-06-06, 公開日: 2014-09-03, 最終更新日: 2024-11-20)

主引用文献

Huang, J.,Kang, B.H.,Pancera, M.,Lee, J.H.,Tong, T.,Feng, Y.,Imamichi, H.,Georgiev, I.S.,Chuang, G.Y.,Druz, A.,Doria-Rose, N.A.,Laub, L.,Sliepen, K.,van Gils, M.J.,de la Pena, A.T.,Derking, R.,Klasse, P.J.,Migueles, S.A.,Bailer, R.T.,Alam, M.,Pugach, P.,Haynes, B.F.,Wyatt, R.T.,Sanders, R.W.,Binley, J.M.,Ward, A.B.,Mascola, J.R.,Kwong, P.D.,Connors, M.
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface.
Nature, 515:138-142, 2014

PubMed Abstract: The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC50) <50 μg ml(-1). The median IC50 of neutralized viruses was 0.033 μg ml(-1), among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

PubMed: 25186731
DOI: 10.1038/nature13601

実験手法

X-RAY DIFFRACTION (1.551 Å)