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Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery

Author

Listed:
  • Vidya Mangala Prasad

    (University of Washington
    Indian Institute of Science)

  • Jelle S. Blijleven

    (University of Groningen)

  • Jolanda M. Smit

    (University of Groningen, University Medical Center Groningen)

  • Kelly K. Lee

    (University of Washington
    University of Washington
    University of Washington)

Abstract

Chikungunya virus (CHIKV) is a human pathogen that delivers its genome to the host cell cytoplasm through endocytic low pH-activated membrane fusion mediated by class-II fusion proteins. Though structures of prefusion, icosahedral CHIKV are available, structural characterization of virion interaction with membranes has been limited. Here, we have used cryo-electron tomography to visualize CHIKV’s complete membrane fusion pathway, identifying key intermediary glycoprotein conformations coupled to membrane remodeling events. Using sub-tomogram averaging, we elucidate features of the low pH-exposed virion, nucleocapsid and full-length E1-glycoprotein’s post-fusion structure. Contrary to class-I fusion systems, CHIKV achieves membrane apposition by protrusion of extended E1-glycoprotein homotrimers into the target membrane. The fusion process also features a large hemifusion diaphragm that transitions to a wide pore for intact nucleocapsid delivery. Our analyses provide comprehensive ultrastructural insights into the class-II virus fusion system function and direct mechanistic characterization of the fundamental process of protein-mediated membrane fusion.

Suggested Citation

  • Vidya Mangala Prasad & Jelle S. Blijleven & Jolanda M. Smit & Kelly K. Lee, 2022. "Visualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32431-9
    DOI: 10.1038/s41467-022-32431-9
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    References listed on IDEAS

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    1. Agata Witkowska & Leonard P. Heinz & Helmut Grubmüller & Reinhard Jahn, 2021. "Tight docking of membranes before fusion represents a metastable state with unique properties," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
    2. Don L. Gibbons & Marie-Christine Vaney & Alain Roussel & Armelle Vigouroux & Brigid Reilly & Jean Lepault & Margaret Kielian & Félix A. Rey, 2004. "Conformational change and protein–protein interactions of the fusion protein of Semliki Forest virus," Nature, Nature, vol. 427(6972), pages 320-325, January.
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