1TJG

Crystal Structure of the broadly neutralizing anti-HIV-1 antibody 2F5 in complex with a gp41 7mer epitope

1TJG の概要

• エントリーDOI: 10.2210/pdb1tjg/pdb
• 関連するPDBエントリー: 1TJH 1TJI 2F5B
• 分子名称: FAB 2F5 Light Chain, FAB 2F5 Heavy Chain, Envelope glycoprotein GP41, ... (6 entities in total)
• 機能のキーワード: 2f5; antibody; gp41; hiv-1; neutralizing; membrane-proximal, viral protein-immune system complex, viral protein/immune system
• 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: 50105.44

構造登録者

Ofek, G.,Tang, M.,Sambor, A.,Katinger, H.,Mascola, J.R.,Wyatt, R.,Kwong, P.D. (登録日: 2004-06-04, 公開日: 2004-10-05, 最終更新日: 2023-08-23)

主引用文献

Ofek, G.,Tang, M.,Sambor, A.,Katinger, H.,Mascola, J.R.,Wyatt, R.,Kwong, P.D.
Structure and mechanistic analysis of the Anti-Human Immunodeficiency Virus Type 1 antibody 2F5 in complex with its gp41 epitope
J.Virol., 78:10724-10737, 2004

PubMed Abstract: The membrane-proximal region of the ectodomain of the gp41 envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is the target of three of the five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures of the antigen-binding fragment for one of these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides of the gp41 membrane-proximal region, at 2.0-, 2.1-, and 2.2-A resolutions, respectively. The structures reveal an extended gp41 conformation, which stretches over 30 A in length. Contacts are made with five complementarity-determining regions of the antibody as well as with nonpolymorphic regions. Only one exclusive charged face of the gp41 epitope is bound by 2F5, while the nonbound face, which is hydrophobic, may be hidden due to occlusion by other portions of the ectodomain. The structures reveal that the 2F5 antibody is uniquely built to bind to an epitope that is proximal to a membrane surface and in a manner mostly unaffected by large-scale steric hindrance. Biochemical studies with proteoliposomes confirm the importance of lipid membrane and hydrophobic context in the binding of 2F5 as well as in the binding of 4E10, another broadly neutralizing antibody that recognizes the membrane-proximal region of gp41. Based on these structural and biochemical results, immunization strategies for eliciting 2F5- and 4E10-like broadly neutralizing anti-HIV-1 antibodies are proposed.

PubMed: 15367639
DOI: 10.1128/JVI.78.19.10724-10737.2004

実験手法

X-RAY DIFFRACTION (2 Å)