6FY1

Crystal structure of a V2p-reactive RV144 vaccine-like antibody, CAP228-16H, in complex with a scaffolded autologous V1V2

6FY1 の概要

• エントリーDOI: 10.2210/pdb6fy1/pdb
• 分子名称: CAP228-16H Heavy Chain, CAP228 Autologous Scaffolded V1V2, CAP228-16H Light Chain (3 entities in total)
• 機能のキーワード: fab, hiv-1 envelope v1v2, immune system
• 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: 122146.47

構造登録者

Wibmer, C.K.,Moore, P.L.,Morris, L. (登録日: 2018-03-10, 公開日: 2018-10-17, 最終更新日: 2024-10-23)

主引用文献

Wibmer, C.K.,Richardson, S.I.,Yolitz, J.,Cicala, C.,Arthos, J.,Moore, P.L.,Morris, L.
Common helical V1V2 conformations of HIV-1 Envelope expose the alpha 4 beta 7 binding site on intact virions.
Nat Commun, 9:4489-4489, 2018

PubMed Abstract: The α4β7 integrin is a non-essential HIV-1 adhesion receptor, bound by the gp120 V1V2 domain, facilitating rapid viral dissemination into gut-associated lymphoid tissues. Antibodies blocking this interaction early in infection can improve disease outcome, and V1V2-targeted antibodies were correlated with moderate efficacy reported from the RV144 HIV-1 vaccine trial. Monoclonal α4β7-blocking antibodies recognise two slightly different helical V2 conformations, and current structural data suggests their binding sites are occluded in prefusion envelope trimers. Here, we report cocrystal structures of two α4β7-blocking antibodies from an infected donor complexed with scaffolded V1V2 or V2 peptides. Both antibodies recognised the same helix-coil V2 conformation as RV144 antibody CH58, identifying a frequently sampled alternative conformation of full-length V1V2. In the context of Envelope, this α-helical form of V1V2 displays highly exposed α4β7-binding sites, potentially providing a functional role for non-native Envelope on virion or infected cell surfaces in HIV-1 dissemination, pathogenesis, and vaccine design.

PubMed: 30367034
DOI: 10.1038/s41467-018-06794-x

実験手法

X-RAY DIFFRACTION (3.132 Å)