6SNC

crystal structure of LN01 Fab in complex with an HIV-1 gp41 peptide

6SNC の概要

• エントリーDOI: 10.2210/pdb6snc/pdb
• 分子名称: LNO1 Light Chain, LNO1 Heavy Chain, Envelope glycoprotein gp160, ... (7 entities in total)
• 機能のキーワード: gp41, antibody, complex, mper, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 105645.07

構造登録者

Caillat, C.,Pinto, D.,Corti, D.,Fenwick, C.,Pantaleo, G.,Weissenhorn, W. (登録日: 2019-08-23, 公開日: 2019-11-06, 最終更新日: 2024-11-20)

主引用文献

Pinto, D.,Fenwick, C.,Caillat, C.,Silacci, C.,Guseva, S.,Dehez, F.,Chipot, C.,Barbieri, S.,Minola, A.,Jarrossay, D.,Tomaras, G.D.,Shen, X.,Riva, A.,Tarkowski, M.,Schwartz, O.,Bruel, T.,Dufloo, J.,Seaman, M.S.,Montefiori, D.C.,Lanzavecchia, A.,Corti, D.,Pantaleo, G.,Weissenhorn, W.
Structural Basis for Broad HIV-1 Neutralization by the MPER-Specific Human Broadly Neutralizing Antibody LN01.
Cell Host Microbe, 26:623-637.e8, 2019

PubMed Abstract: Potent and broadly neutralizing antibodies (bnAbs) are the hallmark of HIV-1 protection by vaccination. The membrane-proximal external region (MPER) of the HIV-1 gp41 fusion protein is targeted by the most broadly reactive HIV-1 neutralizing antibodies. Here, we examine the structural and molecular mechansims of neutralization by anti-MPER bnAb, LN01, which was isolated from lymph-node-derived germinal center B cells of an elite controller and exhibits broad neutralization breadth. LN01 engages both MPER and the transmembrane (TM) region, which together form a continuous helix in complex with LN01. The tilted TM orientation allows LN01 to interact simultaneously with the peptidic component of the MPER epitope and membrane via two specific lipid binding sites of the antibody paratope. Although LN01 carries a high load of somatic mutations, most key residues interacting with the MPER epitope and lipids are germline encoded, lending support for the LN01 epitope as a candidate for lineage-based vaccine development.

PubMed: 31653484
DOI: 10.1016/j.chom.2019.09.016

実験手法

X-RAY DIFFRACTION (3.2 Å)