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Transient opening of trimeric prefusion RSV F proteins

Author

Listed:
  • Morgan S. A. Gilman

    (Geisel School of Medicine at Dartmouth
    University of Texas at Austin)

  • Polina Furmanova-Hollenstein

    (Janssen Infectious Diseases and Vaccines)

  • Gabriel Pascual

    (Janssen Immunosciences, World Without Disease Accelerator)

  • Angélique van ‘t Wout

    (Janssen Vaccines & Prevention B.V
    AlphaBiomics)

  • Johannes P. M. Langedijk

    (Janssen Infectious Diseases and Vaccines)

  • Jason S. McLellan

    (University of Texas at Austin)

Abstract

The respiratory syncytial virus (RSV) F glycoprotein is a class I fusion protein that mediates viral entry and is a major target of neutralizing antibodies. Structures of prefusion forms of RSV F, as well as other class I fusion proteins, have revealed compact trimeric arrangements, yet whether these trimeric forms can transiently open remains unknown. Here, we perform structural and biochemical studies on a recently isolated antibody, CR9501, and demonstrate that it enhances the opening of prefusion-stabilized RSV F trimers. The 3.3 Å crystal structure of monomeric RSV F bound to CR9501, combined with analysis of over 25 previously determined RSV F structures, reveals a breathing motion of the prefusion conformation. We also demonstrate that full-length RSV F trimers transiently open and dissociate on the cell surface. Collectively, these findings have implications for the function of class I fusion proteins, as well as antibody prophylaxis and vaccine development for RSV.

Suggested Citation

  • Morgan S. A. Gilman & Polina Furmanova-Hollenstein & Gabriel Pascual & Angélique van ‘t Wout & Johannes P. M. Langedijk & Jason S. McLellan, 2019. "Transient opening of trimeric prefusion RSV F proteins," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09807-5
    DOI: 10.1038/s41467-019-09807-5
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    Cited by:

    1. Daníelsson, Jón & Macrae, Robert & Uthemann, Andreas, 2022. "Artificial intelligence and systemic risk," Journal of Banking & Finance, Elsevier, vol. 140(C).
    2. Cristancho Triana, Gerson Jaquin, 2023. "Actitud e intención hacia el consumo responsable en los hogares de Bogotá," Revista Tendencias, Universidad de Narino, vol. 24(1), pages 130-154, January.
    3. Ugirumurera, Juliette & Severino, Joseph & Ficenec, Karen & Ge, Yanbo & Wang, Qichao & Williams, Lindy & Chae, Junghoon & Lunacek, Monte & Phillips, Caleb, 2021. "A modeling framework for designing and evaluating curbside traffic management policies at Dallas-Fort Worth International Airport," Transportation Research Part A: Policy and Practice, Elsevier, vol. 153(C), pages 130-150.

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