4RX4

Crystal structure of VH1-46 germline-derived CD4-binding site-directed antibody 8ANC134 in complex with HIV-1 clade A Q842.d12 gp120

4RX4 の概要

• エントリーDOI: 10.2210/pdb4rx4/pdb
• 関連するPDBエントリー: 4RWY
• 分子名称: HIV-1 Clade A Q842.d12 gp120, 8ANC134 Heavy chain, 8ANC134 Light Chain, ... (6 entities in total)
• 機能のキーワード: hiv-1 attachment protein, broadly neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1 (11676); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 178981.49

構造登録者

Zhou, T.,Acharya, P.,Moquin, S.,Kwong, P.D. (登録日: 2014-12-08, 公開日: 2015-07-01, 最終更新日: 2024-11-06)

主引用文献

Zhou, T.,Lynch, R.M.,Chen, L.,Acharya, P.,Wu, X.,Doria-Rose, N.A.,Joyce, M.G.,Lingwood, D.,Soto, C.,Bailer, R.T.,Ernandes, M.J.,Kong, R.,Longo, N.S.,Louder, M.K.,McKee, K.,O'Dell, S.,Schmidt, S.D.,Tran, L.,Yang, Z.,Druz, A.,Luongo, T.S.,Moquin, S.,Srivatsan, S.,Yang, Y.,Zhang, B.,Zheng, A.,Pancera, M.,Kirys, T.,Georgiev, I.S.,Gindin, T.,Peng, H.P.,Yang, A.S.,Mullikin, J.C.,Gray, M.D.,Stamatatos, L.,Burton, D.R.,Koff, W.C.,Cohen, M.S.,Haynes, B.F.,Casazza, J.P.,Connors, M.,Corti, D.,Lanzavecchia, A.,Sattentau, Q.J.,Weiss, R.A.,West, A.P.,Bjorkman, P.J.,Scheid, J.F.,Nussenzweig, M.C.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.
Cell(Cambridge,Mass.), 161:1280-1292, 2015

PubMed Abstract: The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.

PubMed: 26004070
DOI: 10.1016/j.cell.2015.05.007

実験手法

X-RAY DIFFRACTION (3.45 Å)