3U1S

Crystal structure of human Fab PGT145, a broadly reactive and potent HIV-1 neutralizing antibody

3U1S の概要

• エントリーDOI: 10.2210/pdb3u1s/pdb
• 分子名称: Fab PGT145 Light chain, Fab PGT145 Heavy chain, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: igg, broadly neutralizing antibody, hiv-1 gp120, 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: 55672.10

構造登録者

Julien, J.-P.,Diwanji, D.,Burton, D.R.,Wilson, I.A. (登録日: 2011-09-30, 公開日: 2011-12-07, 最終更新日: 2024-11-06)

主引用文献

McLellan, J.S.,Pancera, M.,Carrico, C.,Gorman, J.,Julien, J.P.,Khayat, R.,Louder, R.,Pejchal, R.,Sastry, M.,Dai, K.,O'Dell, S.,Patel, N.,Shahzad-Ul-Hussan, S.,Yang, Y.,Zhang, B.,Zhou, T.,Zhu, J.,Boyington, J.C.,Chuang, G.Y.,Diwanji, D.,Georgiev, I.,Do Kwon, Y.,Lee, D.,Louder, M.K.,Moquin, S.,Schmidt, S.D.,Yang, Z.Y.,Bonsignori, M.,Crump, J.A.,Kapiga, S.H.,Sam, N.E.,Haynes, B.F.,Burton, D.R.,Koff, W.C.,Walker, L.M.,Phogat, S.,Wyatt, R.,Orwenyo, J.,Wang, L.X.,Arthos, J.,Bewley, C.A.,Mascola, J.R.,Nabel, G.J.,Schief, W.R.,Ward, A.B.,Wilson, I.A.,Kwong, P.D.
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
Nature, 480:336-343, 2011

PubMed Abstract: Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary sequence diversity and N-linked glycosylation. Human antibodies such as PG9 nonetheless engage V1/V2 and neutralize 80% of HIV-1 isolates. Here we report the structure of V1/V2 in complex with PG9. V1/V2 forms a four-stranded β-sheet domain, in which sequence diversity and glycosylation are largely segregated to strand-connecting loops. PG9 recognition involves electrostatic, sequence-independent and glycan interactions: the latter account for over half the interactive surface but are of sufficiently weak affinity to avoid autoreactivity. The structures of V1/V2-directed antibodies CH04 and PGT145 indicate that they share a common mode of glycan penetration by extended anionic loops. In addition to structurally defining V1/V2, the results thus identify a paradigm of antibody recognition for highly glycosylated antigens, which-with PG9-involves a site of vulnerability comprising just two glycans and a strand.

PubMed: 22113616
DOI: 10.1038/nature10696

実験手法

X-RAY DIFFRACTION (2.3 Å)