8WNP

ZIKV rsNS1 in complex with Fab AA12 and anti-fab nanobody

Summary for 8WNP

• Entry DOI: 10.2210/pdb8wnp/pdb
• Related: 8WN8
• EMDB information: 37670
• Descriptor: VL Chains, VH Chains, Non-structural protein 1, ... (5 entities in total)
• Functional Keywords: antibody, flavivirus, zika, cryoem, non structural protein 1, ns1, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 8
• Total formula weight: 201371.07

Authors

Chew, B.L.A.,Luo, D. (deposition date: 2023-10-06, release date: 2024-05-08, Last modification date: 2025-05-14)

Primary citation

Chew, B.L.A.,Ngoh, A.Q.,Phoo, W.W.,Weng, M.J.G.,Sheng, H.J.,Chan, K.W.K.,Tan, E.Y.J.,Gelbart, T.,Xu, C.,Tan, G.S.,Vasudevan, S.G.,Luo, D.
Structural basis of Zika virus NS1 multimerization and human antibody recognition.
Npj Viruses, 2:14-14, 2024

PubMed Abstract: Zika virus (ZIKV) belongs to the Flavivirus genus of the Flaviviridae family along with the four serotypes of dengue virus (DENV1-4). The recent global outbreaks of contemporary ZIKV strains demonstrated that infection can lead to neurological sequelae in adults and severe abnormalities in newborns that were previously unreported with ancestral strains. As such, there remains an unmet need for efficacious vaccines and antiviral agents against ZIKV. The non-structural protein 1 (NS1) is secreted from the infected cell and is thought to be associated with disease severity besides its proven usefulness for differential diagnoses. However, its physiologically relevant structure and pathogenesis mechanisms remain unclear. Here, we present high-resolution cryoEM structures of ZIKV recombinant secreted NS1 (rsNS1) and its complexes with three human monoclonal antibodies (AA12, EB9, GB5), as well as evidence for ZIKV infection-derived secreted NS1 (isNS1) binding to High Density Lipoprotein (HDL). We show that ZIKV rsNS1 forms tetramers and filamentous repeats of tetramers. We also observed that antibody binding did not disrupt the ZIKV NS1 tetramers as they bound to the wing and connector subdomain of the β-ladder. Our study reveals new insights into NS1 multimerization, highlights the need to distinguish the polymorphic nature of rsNS1 and isNS1, and expands the mechanistic basis of the protection conferred by antibodies targeting NS1.

PubMed: 40295651
DOI: 10.1038/s44298-024-00024-6

Experimental method

ELECTRON MICROSCOPY (3.1 Å)