5I8E

Crystal Structure of Broadly Neutralizing HIV-1 Fusion Peptide-Targeting Antibody VRC34.01 Fab

5I8E の概要

• エントリーDOI: 10.2210/pdb5i8e/pdb
• 関連するPDBエントリー: 5I8C 5I8H
• 分子名称: VRC34.01 Fab heavy chain, VRC34.01 Fab light chain, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hiv-1, envelope, trimer, fusion peptide, antibody, neutralizing, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93751.99

構造登録者

Xu, K.,Zhou, T.,Liu, K.,Kwong, P.D. (登録日: 2016-02-18, 公開日: 2016-05-25, 最終更新日: 2024-10-30)

主引用文献

Kong, R.,Xu, K.,Zhou, T.,Acharya, P.,Lemmin, T.,Liu, K.,Ozorowski, G.,Soto, C.,Taft, J.D.,Bailer, R.T.,Cale, E.M.,Chen, L.,Choi, C.W.,Chuang, G.Y.,Doria-Rose, N.A.,Druz, A.,Georgiev, I.S.,Gorman, J.,Huang, J.,Joyce, M.G.,Louder, M.K.,Ma, X.,McKee, K.,O'Dell, S.,Pancera, M.,Yang, Y.,Blanchard, S.C.,Mothes, W.,Burton, D.R.,Koff, W.C.,Connors, M.,Ward, A.B.,Kwong, P.D.,Mascola, J.R.
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.
Science, 352:828-833, 2016

PubMed Abstract: The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.

PubMed: 27174988
DOI: 10.1126/science.aae0474

実験手法

X-RAY DIFFRACTION (2.655 Å)