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bioRxiv · 10.1101/2022.04.04.487075

CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever

Shu, B.·Ooi, J.·Tan, A.·Ng, T.-S.·Dejnirattisai, W.·Mongkolsapaya, J.·Fibriansah, G.·Shi, J.·Kostyuchenko, V.·Screaton, G.·Lok, S.-M.
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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, the extracellular multi-oligomeric secreted NS1 (sNS1) is a major factor contributing to DHF. The structure of the iNS1 is well studied but not sNS1. Here we show the tetrameric (stable and loose conformation) and hexameric structures of sNS1. 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.

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Shu, B., Ooi, J., Tan, A., Ng, T.-S., Dejnirattisai, W., Mongkolsapaya, J., Fibriansah, G., Shi, J., Kostyuchenko, V., Screaton, G., Lok, S.-M.. 2022-04-05. CryoEM structures of the multimeric secreted NS1, a major factor for dengue hemorrhagic fever. https://doi.org/10.1101/2022.04.04.487075

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