6FY0

Crystal structure of a V2-directed, RV144 vaccine-like antibody from HIV-1 infection, CAP228-16H, bound to a heterologous V2 peptide

6FY0 の概要

• エントリーDOI: 10.2210/pdb6fy0/pdb
• 分子名称: CAP228-16H Heavy Chain, CAP228-16H Light Chain, CAP45 V2 peptide, ... (5 entities in total)
• 機能のキーワード: fab, hiv v2 peptide, 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: 100466.34

構造登録者

Wibmer, C.K.,Fernandes, M.,Vijayakumar, B.,Dirr, H.W.,Sayed, Y.,Moore, P.L.,Morris, L. (登録日: 2018-03-10, 公開日: 2018-11-21, 最終更新日: 2024-11-13)

主引用文献

van Eeden, C.,Wibmer, C.K.,Scheepers, C.,Richardson, S.I.,Nonyane, M.,Lambson, B.,Mkhize, N.N.,Vijayakumar, B.,Sheng, Z.,Stanfield-Oakley, S.,Bhiman, J.N.,Bekker, V.,Hermanus, T.,Mabvakure, B.,Ismail, A.,Moody, M.A.,Wiehe, K.,Garrett, N.,Karim, S.A.,Dirr, H.,Fernandes, M.A.,Sayed, Y.,Shapiro, L.,Ferrari, G.,Haynes, B.F.,Moore, P.L.,Morris, L.
V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.
Cell Rep, 25:3123-3135.e6, 2018

PubMed Abstract: Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. A cocrystal structure of CAP228-16H bound to a V2 peptide identified a IGLV3-21 gene-encoded DDxD motif that is used to bind K169, with a mechanism that allows CAP228-16H to recognize more globally relevant V2 immunotypes. Overall, these data further our understanding of the development of cross-reactive, V2-binding, antiviral antibodies and effectively expand the human light chain repertoire able to respond to RV144-like immunogens.

PubMed: 30540944
DOI: 10.1016/j.celrep.2018.11.058

実験手法

X-RAY DIFFRACTION (2.57 Å)