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

Seamus R. Morrone; Valerie S.Y. Chew; Xin Ni Lim; Thiam Seng Ng; Victor A. Kostyuchenko; Shuijun Zhang; Melissa Wirawan; Pau Ling Chew; Jaime Lee; Joanne L. Tan; Jiaqi Wang; Ter Yong Tan; Jian Shi; Gavin Screaton; Marc C. Morais; Shee Mei Lok

doi:10.1038/s41467-020-16925-y

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

Seamus R. Morrone, Valerie S.Y. Chew, Xin Ni Lim, Thiam Seng Ng, Victor A. Kostyuchenko, Shuijun Zhang, Melissa Wirawan, Pau Ling Chew, Jaime Lee, Joanne L. Tan, Jiaqi Wang, Ter Yong Tan, Jian Shi, Gavin Screaton, Marc C. Morais, Shee Mei Lok

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

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 ~10 Å 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.

Original language	English (US)
Article number	3112
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-16925-y
State	Published - Dec 1 2020
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-020-16925-y

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Morrone, S. R., Chew, V. S. Y., Lim, X. N., Ng, T. S., Kostyuchenko, V. A., Zhang, S., Wirawan, M., Chew, P. L., Lee, J., Tan, J. L., Wang, J., Tan, T. Y., Shi, J., Screaton, G., Morais, M. C., & Lok, S. M. (2020). High flavivirus structural plasticity demonstrated by a non-spherical morphological variant. Nature communications, 11(1), Article 3112. https://doi.org/10.1038/s41467-020-16925-y

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abstract = "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 ~10 {\AA} 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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AU - Lee, Jaime

AU - Tan, Joanne L.

AU - Wang, Jiaqi

AU - Tan, Ter Yong

AU - Shi, Jian

AU - Screaton, Gavin

AU - Morais, Marc C.

AU - Lok, Shee Mei

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

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