7wus
CryoEM structure of a dimer of loose sNS1 tetramer
Structural highlights
FunctionD3XNS4_9FLAV Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.[ARBA:ARBA00024317] Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Publication Abstract from PubMedDengue 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 beta-sheet or beta-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. CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever.,Shu B, Ooi JSG, Tan AWK, Ng TS, Dejnirattisai W, Mongkolsapaya J, Fibriansah G, Shi J, Kostyuchenko VA, Screaton GR, Lok SM Nat Commun. 2022 Nov 9;13(1):6756. doi: 10.1038/s41467-022-34415-1. PMID:36347841[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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