7RI2

Crystal structure of anti-HIV llama VHH antibody A12 in complex with HIV-1 C1086 gp120

7RI2 の概要

• エントリーDOI: 10.2210/pdb7ri2/pdb
• 関連するPDBエントリー: 7R73
• 分子名称: Glycoprotein 120, anti-HIV llama VHH antibody A12, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: llama, antibody, vhh, hiv-1, gp120, immune system
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 59982.78

構造登録者

Zhou, T.,Kwong, P.D. (登録日: 2021-07-19, 公開日: 2022-03-30, 最終更新日: 2024-10-16)

主引用文献

Zhou, T.,Chen, L.,Gorman, J.,Wang, S.,Kwon, Y.D.,Lin, B.C.,Louder, M.K.,Rawi, R.,Stancofski, E.D.,Yang, Y.,Zhang, B.,Quigley, A.F.,McCoy, L.E.,Rutten, L.,Verrips, T.,Weiss, R.A.,Doria-Rose, N.A.,Shapiro, L.,Kwong, P.D.
Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.
Structure, 30:862-875.e4, 2022

PubMed Abstract: Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env.

PubMed: 35413243
DOI: 10.1016/j.str.2022.03.012

実験手法

X-RAY DIFFRACTION (2.8 Å)