4OCW

Crystal structure of human Fab CAP256-VRC26.06, a potent V1V2-directed HIV-1 neutralizing antibody

4OCW の概要

• エントリーDOI: 10.2210/pdb4ocw/pdb
• 関連するPDBエントリー: 4OCR 4OCS 4OD1 4OD3 4ODH 4ORG
• 分子名称: CAP256-VRC26.06 light chain, CAP256-VRC26.06 heavy chain (2 entities in total)
• 機能のキーワード: fab, hiv-1, v1v2, cap256, vrc26, 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: 50486.23

構造登録者

Gorman, J.,Doria-Rose, N.A.,Schramm, C.A.,Moore, P.L.,Mascola, J.R.,Shapiro, L.,Morris, L.,Kwong, P.D. (登録日: 2014-01-09, 公開日: 2014-02-26, 最終更新日: 2024-10-09)

主引用文献

Doria-Rose, N.A.,Schramm, C.A.,Gorman, J.,Moore, P.L.,Bhiman, J.N.,Dekosky, B.J.,Ernandes, M.J.,Georgiev, I.S.,Kim, H.J.,Pancera, M.,Staupe, R.P.,Altae-Tran, H.R.,Bailer, R.T.,Crooks, E.T.,Cupo, A.,Druz, A.,Garrett, N.J.,Hoi, K.H.,Kong, R.,Louder, M.K.,Longo, N.S.,McKee, K.,Nonyane, M.,O'Dell, S.,Roark, R.S.,Rudicell, R.S.,Schmidt, S.D.,Sheward, D.J.,Soto, C.,Wibmer, C.K.,Yang, Y.,Zhang, Z.,Sequencing, Nisc Comparative,Mullikin, J.C.,Binley, J.M.,Sanders, R.W.,Wilson, I.A.,Moore, J.P.,Ward, A.B.,Georgiou, G.,Williamson, C.,Abdool Karim, S.S.,Morris, L.,Kwong, P.D.,Shapiro, L.,Mascola, J.R.
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.
Nature, 509:55-62, 2014

PubMed Abstract: Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.

PubMed: 24590074
DOI: 10.1038/nature13036

実験手法

X-RAY DIFFRACTION (3.001 Å)