5FEH

Crystal structure of PCT64_35B, a broadly neutralizing anti-HIV antibody

5FEH の概要

• エントリーDOI: 10.2210/pdb5feh/pdb
• 分子名称: PCT64_26 Fab light chain, PCT64_26 Fab heavy chain, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hiv, broadly neutralizing antibody, v1/v2, 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: 150003.92

構造登録者

Murrell, S.,Wilson, I.A. (登録日: 2015-12-17, 公開日: 2017-08-16, 最終更新日: 2024-10-23)

主引用文献

Landais, E.,Murrell, B.,Briney, B.,Murrell, S.,Rantalainen, K.,Berndsen, Z.T.,Ramos, A.,Wickramasinghe, L.,Smith, M.L.,Eren, K.,de Val, N.,Wu, M.,Cappelletti, A.,Umotoy, J.,Lie, Y.,Wrin, T.,Algate, P.,Chan-Hui, P.Y.,Karita, E.,Ward, A.B.,Wilson, I.A.,Burton, D.R.,Smith, D.,Pond, S.L.K.,Poignard, P.
HIV Envelope Glycoform Heterogeneity and Localized Diversity Govern the Initiation and Maturation of a V2 Apex Broadly Neutralizing Antibody Lineage.
Immunity, 47:990-1003.e9, 2017

PubMed Abstract: Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions. The data suggested a role for Env glycoform heterogeneity in the activation of the lineage germline B cell. Finally, we showed that localized diversity at key V2 epitope residues drove bnAb maturation toward breadth, mirroring the Env evolution pattern described for another donor who developed V2-apex targeting bnAbs. Overall, these findings suggest potential strategies for vaccine approaches based on germline-targeting and serial immunogen design.

PubMed: 29166592
DOI: 10.1016/j.immuni.2017.11.002

実験手法

X-RAY DIFFRACTION (3.1 Å)