4DQO

Crystal Structure of PG16 Fab in Complex with V1V2 Region from HIV-1 strain ZM109

4DQO の概要

• エントリーDOI: 10.2210/pdb4dqo/pdb
• 関連するPDBエントリー: 3MME 3MUG 3U2S
• 分子名称: PG16 Fab Heavy Chain, PG16 Fab Light Chain, 1FD6-V1V2 scaffold ZM109 HIV-1 strain, ... (6 entities in total)
• 機能のキーワード: immunoglobulin, immune recognition, immune system, glycan, hiv-1, v1v2, envelope glycoprotein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 66160.91

構造登録者

Pancera, M.,McLellan, J.S.,Kwong, P.D. (登録日: 2012-02-16, 公開日: 2013-03-06, 最終更新日: 2024-10-16)

主引用文献

Pancera, M.,Shahzad-Ul-Hussan, S.,Doria-Rose, N.A.,McLellan, J.S.,Bailer, R.T.,Dai, K.,Loesgen, S.,Louder, M.K.,Staupe, R.P.,Yang, Y.,Zhang, B.,Parks, R.,Eudailey, J.,Lloyd, K.E.,Blinn, J.,Alam, S.M.,Haynes, B.F.,Amin, M.N.,Wang, L.X.,Burton, D.R.,Koff, W.C.,Nabel, G.J.,Mascola, J.R.,Bewley, C.A.,Kwong, P.D.
Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16.
Nat.Struct.Mol.Biol., 20:804-813, 2013

PubMed Abstract: HIV-1 uses a diverse N-linked-glycan shield to evade recognition by antibody. Select human antibodies, such as the clonally related PG9 and PG16, recognize glycopeptide epitopes in the HIV-1 V1-V2 region and penetrate this shield, but their ability to accommodate diverse glycans is unclear. Here we report the structure of antibody PG16 bound to a scaffolded V1-V2, showing an epitope comprising both high mannose-type and complex-type N-linked glycans. We combined structure, NMR and mutagenesis analyses to characterize glycan recognition by PG9 and PG16. Three PG16-specific residues, arginine, serine and histidine (RSH), were critical for binding sialic acid on complex-type glycans, and introduction of these residues into PG9 produced a chimeric antibody with enhanced HIV-1 neutralization. Although HIV-1-glycan diversity facilitates evasion, antibody somatic diversity can overcome this and can provide clues to guide the design of modified antibodies with enhanced neutralization.

PubMed: 23708607
DOI: 10.1038/nsmb.2600

実験手法

X-RAY DIFFRACTION (2.438 Å)