7WUS

CryoEM structure of a dimer of loose sNS1 tetramer

7WUS の概要

• エントリーDOI: 10.2210/pdb7wus/pdb
• EMDBエントリー: 32840
• 分子名称: Core protein (1 entity in total)
• 機能のキーワード: ns1 protein, viral protein
• 由来する生物種: Dengue virus 2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77750.43

構造登録者

Shu, B.,Lok, S.M. (登録日: 2022-02-09, 公開日: 2022-12-21, 最終更新日: 2024-11-06)

主引用文献

Shu, B.,Ooi, J.S.G.,Tan, A.W.K.,Ng, T.S.,Dejnirattisai, W.,Mongkolsapaya, J.,Fibriansah, G.,Shi, J.,Kostyuchenko, V.A.,Screaton, G.R.,Lok, S.M.
CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever.
Nat Commun, 13:6756-6756, 2022

PubMed Abstract: Dengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional. The intracellular dimeric NS1 (iNS1) forms part of the viral replication complex. Previous studies suggest the extracellular secreted NS1 (sNS1), which is a major factor contributing to DHF, exists as hexamers. The structure of the iNS1 is well-characterised but not that of sNS1. Here we show by cryoEM that the recombinant sNS1 exists in multiple oligomeric states: the tetrameric (stable and loose conformation) and hexameric structures. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain - elongated β-sheet or β-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.

PubMed: 36347841
DOI: 10.1038/s41467-022-34415-1

実験手法

ELECTRON MICROSCOPY (3.4 Å)