8WO4

ZIKV rsNS1 in complex with Fab EB9 and anti-fab nanobody

8WO4 の概要

• エントリーDOI: 10.2210/pdb8wo4/pdb
• 関連するPDBエントリー: 8WN8 8WNP 8WNU 8WO0
• EMDBエントリー: 37678
• 分子名称: VL, VH, Non-structural protein 1, ... (5 entities in total)
• 機能のキーワード: antibody, flavivirus, zika, cryoem, non structural protein 1, ns1, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 208220.32

構造登録者

Chew, B.L.A.,Luo, D. (登録日: 2023-10-06, 公開日: 2024-05-08, 最終更新日: 2025-05-14)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.8 Å)