4.8 Article

High flavivirus structural plasticity demonstrated by a non-spherical morphological variant

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NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-020-16925-y

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资金

  1. National Research Foundation Investigatorship award [NRF-NRFI2016-01]
  2. National Research Foundation competitive Research Project [NRF2016NRF-CRP001-063]
  3. Duke-NUS Signature Research Programme - Ministry of Health, Singapore
  4. Public Health Service grants from the National Institutes of Health, USA [GM122979, GM127365]

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Previous flavivirus (dengue and Zika viruses) studies showed largely spherical particles either with smooth or bumpy surfaces. Here, we demonstrate flavivirus particles have high structural plasticity by the induction of a non-spherical morphology at elevated temperatures: the club-shaped particle (clubSP), which contains a cylindrical tail and a disc-like head. Complex formation of DENV and ZIKV with Fab C10 stabilize the viruses allowing cryoEM structural determination to similar to 10 angstrom resolution. The caterpillar-shaped (catSP) Fab C10:ZIKV complex shows Fabs locking the E protein raft structure containing three E dimers. However, compared to the original spherical structure, the rafts have rotated relative to each other. The helical tail structure of Fab C10:DENV3 clubSP showed although the Fab locked an E protein dimer, the dimers have shifted laterally. Morphological diversity, including clubSP and the previously identified bumpy and smooth-surfaced spherical particles, may help flavivirus survival and immune evasion.

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