7BSC

Complex structure of 1G5.3 Fab bound to DENV2 NS1c

Summary for 7BSC

• Entry DOI: 10.2210/pdb7bsc/pdb
• Descriptor: Non-structural protein 1, 1G5.3 Fab Heavy Chain, 1G5.3 Fab Light Chain, ... (4 entities in total)
• Functional Keywords: dengue virus, ns1, antibody, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Dengue virus 2; More
• Total number of polymer chains: 3
• Total formula weight: 68666.06

Authors

Song, H.,Qi, J.,Gao, F.G. (deposition date: 2020-03-30, release date: 2020-12-23, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.31 Å)