6PLK

Crystal structure of ZIKV-116 Fab in complex with ZIKV envelope DIII

6PLK の概要

• エントリーDOI: 10.2210/pdb6plk/pdb
• 分子名称: ZIKV-116 heavy chain, ZIKV-116 light chain, Env, ... (4 entities in total)
• 機能のキーワード: human antibody, zikv-diii, antiviral protein, structural genomics, center for structural genomics of infectious diseases, csgid
• 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: 118949.84

構造登録者

Zhao, H.,Fremont, D.H.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2019-07-01, 公開日: 2019-11-20, 最終更新日: 2024-11-13)

主引用文献

Zhao, H.,Xu, L.,Bombardi, R.,Nargi, R.,Deng, Z.,Errico, J.M.,Nelson, C.A.,Dowd, K.A.,Pierson, T.C.,Crowe, J.E.,Diamond, M.S.,Fremont, D.H.
Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge.
J.Exp.Med., 217:-, 2020

PubMed Abstract: We previously generated a panel of human monoclonal antibodies (mAbs) against Zika virus (ZIKV) and identified one, ZIKV-116, that shares germline usage with mAbs identified in multiple donors. Here we show that ZIKV-116 interferes with ZIKV infection at a post-cellular attachment step by blocking viral fusion with host membranes. ZIKV-116 recognizes the lateral ridge of envelope protein domain III, with one critical residue varying between the Asian and African strains responsible for differential binding affinity and neutralization potency (E393D). ZIKV-116 also binds to and cross-neutralizes some dengue virus serotype 1 (DENV1) strains, with genotype-dependent inhibition explained by variation in a domain II residue (R204K) that potentially modulates exposure of the distally located, partially cryptic epitope. The V-J reverted germline configuration of ZIKV-116 preferentially binds to and neutralizes an Asian ZIKV strain, suggesting that this epitope may optimally induce related B cell clonotypes. Overall, these studies provide a structural and molecular mechanism for a cross-reactive mAb that uniquely neutralizes ZIKV and DENV1.

PubMed: 31757867
DOI: 10.1084/jem.20191792

実験手法

X-RAY DIFFRACTION (2.3 Å)