4JAM

Crystal structure of broadly neutralizing anti-hiv-1 antibody ch103

4JAM の概要

• エントリーDOI: 10.2210/pdb4jam/pdb
• 関連するPDBエントリー: 4JAN
• 分子名称: ANTIGEN BINDING FRAGMENT OF HEAVY CHAIN of CH103, ANTIGEN BINDING FRAGMENT OF LIGHT CHAIN of CH103, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: neutralization, vaccine, hiv-1, antibody, immunoglobulin, 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: 95235.43

構造登録者

Zhou, T.,Moquin, S.,Zheng, A.,Srivatsan, S.,Kwong, P.D. (登録日: 2013-02-18, 公開日: 2013-04-03, 最終更新日: 2024-11-27)

主引用文献

Liao, H.X.,Lynch, R.,Zhou, T.,Gao, F.,Alam, S.M.,Boyd, S.D.,Fire, A.Z.,Roskin, K.M.,Schramm, C.A.,Zhang, Z.,Zhu, J.,Shapiro, L.,Mullikin, J.C.,Gnanakaran, S.,Hraber, P.,Wiehe, K.,Kelsoe, G.,Yang, G.,Xia, S.M.,Montefiori, D.C.,Parks, R.,Lloyd, K.E.,Scearce, R.M.,Soderberg, K.A.,Cohen, M.,Kamanga, G.,Louder, M.K.,Tran, L.M.,Chen, Y.,Cai, F.,Chen, S.,Moquin, S.,Du, X.,Joyce, M.G.,Srivatsan, S.,Zhang, B.,Zheng, A.,Shaw, G.M.,Hahn, B.H.,Kepler, T.B.,Korber, B.T.,Kwong, P.D.,Mascola, J.R.,Haynes, B.F.
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.
Nature, 496:469-476, 2013

PubMed Abstract: Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.

PubMed: 23552890
DOI: 10.1038/nature12053

実験手法

X-RAY DIFFRACTION (1.65 Å)