6UBI

N123-VRC34.05 HIV neutralizing antibody in complex with HIV fusion peptide residue 512-519

6UBI の概要

• エントリーDOI: 10.2210/pdb6ubi/pdb
• 分子名称: VRC34.05 heavy chain, VRC34.05 light chain, HIV fusion peptide 512-519, ... (4 entities in total)
• 機能のキーワード: hiv, neutralizing, antibody, fusion peptide, immune system-viral protein, immune system-viral protein complex, immune system/viral protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 97006.31

構造登録者

Xu, K.,Liu, K.,Kwong, P.D. (登録日: 2019-09-11, 公開日: 2020-03-18, 最終更新日: 2020-04-22)

主引用文献

Shen, C.H.,DeKosky, B.J.,Guo, Y.,Xu, K.,Gu, Y.,Kilam, D.,Ko, S.H.,Kong, R.,Liu, K.,Louder, M.K.,Ou, L.,Zhang, B.,Chao, C.W.,Corcoran, M.M.,Feng, E.,Huang, J.,Normandin, E.,O'Dell, S.,Ransier, A.,Rawi, R.,Sastry, M.,Schmidt, S.D.,Wang, S.,Wang, Y.,Chuang, G.Y.,Doria-Rose, N.A.,Lin, B.,Zhou, T.,Boritz, E.A.,Connors, M.,Douek, D.C.,Karlsson Hedestam, G.B.,Sheng, Z.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.
Cell Host Microbe, 27:531-, 2020

PubMed Abstract: Rare mutations have been proposed to restrict the development of broadly neutralizing antibodies against HIV-1, but this has not been explicitly demonstrated. We hypothesized that such rare mutations might be identified by comparing broadly neutralizing and non-broadly neutralizing branches of an antibody-developmental tree. Because sequences of antibodies isolated from the fusion peptide (FP)-targeting VRC34-antibody lineage suggested it might be suitable for such rare mutation analysis, we carried out next-generation sequencing (NGS) on B cell transcripts from donor N123, the source of the VRC34 lineage, and functionally and structurally characterized inferred intermediates along broadly neutralizing and poorly neutralizing developmental branches. The broadly neutralizing VRC34.01 branch required the rare heavy-chain mutation Y33P to bind FP, whereas the early bifurcated VRC34.05 branch did not require this rare mutation and evolved less breadth. Our results demonstrate how a required rare mutation can restrict development and shape the maturation of a broad HIV-1-neutralizing antibody lineage.

PubMed: 32130953
DOI: 10.1016/j.chom.2020.01.027

実験手法

X-RAY DIFFRACTION (1.903 Å)