7BSD

Complex structure of 1G5.3 Fab bound to ZIKV NS1c

7BSD の概要

• エントリーDOI: 10.2210/pdb7bsd/pdb
• 分子名称: 1G5.3 Fab Heavy Chain, 1G5.3 Fab Light Chain, NS1C, ... (4 entities in total)
• 機能のキーワード: zika virus, ns1, antibody, viral protein, immune system-viral protein complex, immune system/viral protein
• 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: 137888.75

構造登録者

Song, H.,Qi, J.,Gao, F.G. (登録日: 2020-03-30, 公開日: 2020-12-23, 最終更新日: 2024-10-23)

主引用文献

Modhiran, N.,Song, H.,Liu, L.,Bletchly, C.,Brillault, L.,Amarilla, A.A.,Xu, X.,Qi, J.,Chai, Y.,Cheung, S.T.M.,Traves, R.,Setoh, Y.X.,Bibby, S.,Scott, C.A.P.,Freney, M.E.,Newton, N.D.,Khromykh, A.A.,Chappell, K.J.,Muller, D.A.,Stacey, K.J.,Landsberg, M.J.,Shi, Y.,Gao, G.F.,Young, P.R.,Watterson, D.
A broadly protective antibody that targets the flavivirus NS1 protein.
Science, 371:190-194, 2021

PubMed Abstract: There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeutic application of 1G5.3 reduces viremia and improves survival in dengue, Zika, and West Nile virus murine models. Finally, we demonstrate that 1G5.3 protection is independent of effector function, identifying the 1G5.3 epitope as a key site for broad-spectrum antiviral development.

PubMed: 33414219
DOI: 10.1126/science.abb9425

実験手法

X-RAY DIFFRACTION (2.53 Å)