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-Structure paper
タイトル | CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 6756, Year 2022 |
掲載日 | 2022年11月9日 |
著者 | Bo Shu / Justin S G Ooi / Aaron W K Tan / Thiam-Seng Ng / Wanwisa Dejnirattisai / Juthathip Mongkolsapaya / Guntur Fibriansah / Jian Shi / Victor A Kostyuchenko / Gavin R Screaton / Shee-Mei Lok / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:36347841 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.4 - 8.3 Å |
構造データ | EMDB-32839, PDB-7wur: EMDB-32840, PDB-7wus: EMDB-32841, PDB-7wut: EMDB-32842, PDB-7wuu: EMDB-32843, PDB-7wuv: |
由来 |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / NS1 / Complex / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex / NS1 protein |