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Functional refolding of the penetration protein on a non-enveloped virus

Author

Listed:
  • Tobias Herrmann

    (Harvard Medical School
    Harvard Medical School)

  • Raúl Torres

    (Boston Children’s Hospital)

  • Eric N. Salgado

    (Boston Children’s Hospital
    Seqirus USA)

  • Cristina Berciu

    (Brandeis University
    McLean Hospital)

  • Daniel Stoddard

    (Brandeis University
    University of Texas Southwestern)

  • Daniela Nicastro

    (Brandeis University
    University of Texas Southwestern)

  • Simon Jenni

    (Harvard Medical School)

  • Stephen C. Harrison

    (Harvard Medical School
    Boston Children’s Hospital
    Harvard Medical School)

Abstract

A non-enveloped virus requires a membrane lesion to deliver its genome into a target cell1. For rotaviruses, membrane perforation is a principal function of the viral outer-layer protein, VP42,3. Here we describe the use of electron cryomicroscopy to determine how VP4 performs this function and show that when activated by cleavage to VP8* and VP5*, VP4 can rearrange on the virion surface from an ‘upright’ to a ‘reversed’ conformation. The reversed structure projects a previously buried ‘foot’ domain outwards into the membrane of the host cell to which the virion has attached. Electron cryotomograms of virus particles entering cells are consistent with this picture. Using a disulfide mutant of VP4, we have also stabilized a probable intermediate in the transition between the two conformations. Our results define molecular mechanisms for the first steps of the penetration of rotaviruses into the membranes of target cells and suggest similarities with mechanisms postulated for other viruses.

Suggested Citation

  • Tobias Herrmann & Raúl Torres & Eric N. Salgado & Cristina Berciu & Daniel Stoddard & Daniela Nicastro & Simon Jenni & Stephen C. Harrison, 2021. "Functional refolding of the penetration protein on a non-enveloped virus," Nature, Nature, vol. 590(7847), pages 666-670, February.
    • Handle: RePEc:nat:nature:v:590:y:2021:i:7847:d:10.1038_s41586-020-03124-4
    DOI: 10.1038/s41586-020-03124-4
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    Cited by:

    1. Liya Hu & Wilhelm Salmen & Rong Chen & Yi Zhou & Frederick Neill & James E. Crowe & Robert L. Atmar & Mary K. Estes & B. V. Venkataram Prasad, 2022. "Atomic structure of the predominant GII.4 human norovirus capsid reveals novel stability and plasticity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Zhiqiang Li & Han Xia & Guibo Rao & Yan Fu & Tingting Chong & Kexing Tian & Zhiming Yuan & Sheng Cao, 2024. "Cryo-EM structures of Banna virus in multiple states reveal stepwise detachment of viral spikes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. Simon Jenni & Joshua A. Horwitz & Louis-Marie Bloyet & Sean P. J. Whelan & Stephen C. Harrison, 2022. "Visualizing molecular interactions that determine assembly of a bullet-shaped vesicular stomatitis virus particle," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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