IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32431-9.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32431-9
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32431-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    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. Donald J. Benton & Steven J. Gamblin & Peter B. Rosenthal & John J. Skehel, 2020. "Structural transitions in influenza haemagglutinin at membrane fusion pH," Nature, Nature, vol. 583(7814), pages 150-153, July.
    3. James E. Voss & Marie-Christine Vaney & Stéphane Duquerroy & Clemens Vonrhein & Christine Girard-Blanc & Elodie Crublet & Andrew Thompson & Gérard Bricogne & Félix A. Rey, 2010. "Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography," Nature, Nature, vol. 468(7324), pages 709-712, December.
    4. 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.
    5. Long Li & Joyce Jose & Ye Xiang & Richard J. Kuhn & Michael G. Rossmann, 2010. "Structural changes of envelope proteins during alphavirus fusion," Nature, Nature, vol. 468(7324), pages 705-708, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Xiaofeng Zhai & Xiaoling Li & Michael Veit & Ningning Wang & Yu Wang & Andres Merits & Zhiwen Jiang & Yan Qin & Xiaoguang Zhang & Kaili Qi & Houqi Jiao & Wan-Ting He & Ye Chen & Yang Mao & Shuo Su, 2024. "LDLR is used as a cell entry receptor by multiple alphaviruses," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. David Moi & Shunsuke Nishio & Xiaohui Li & Clari Valansi & Mauricio Langleib & Nicolas G. Brukman & Kateryna Flyak & Christophe Dessimoz & Daniele de Sanctis & Kathryn Tunyasuvunakool & John Jumper & , 2022. "Discovery of archaeal fusexins homologous to eukaryotic HAP2/GCS1 gamete fusion proteins," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Ningning Wang & Andres Merits & Michael Veit & Laura Sandra Lello & Shuhan Kong & Houqi Jiao & Jie Chen & Yu Wang & Georgi Dobrikov & Félix A. Rey & Shuo Su, 2024. "LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy," Nature Communications, Nature, vol. 15(1), pages 1-7, December.
    4. Marie-Christine Vaney & Mariano Dellarole & Stéphane Duquerroy & Iris Medits & Georgios Tsouchnikas & Alexander Rouvinski & Patrick England & Karin Stiasny & Franz X. Heinz & Félix A. Rey, 2022. "Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    5. Samantha Hover & Frank W. Charlton & Jan Hellert & Jessica J. Swanson & Jamel Mankouri & John N. Barr & Juan Fontana, 2023. "Organisation of the orthobunyavirus tripodal spike and the structural changes induced by low pH and K+ during entry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Pan Yang & Wanyu Li & Xiaoyi Fan & Junhua Pan & Colin J. Mann & Haley Varnum & Lars E. Clark & Sarah A. Clark & Adrian Coscia & Himanish Basu & Katherine Nabel Smith & Vesna Brusic & Jonathan Abraham, 2024. "Structural basis for VLDLR recognition by eastern equine encephalitis virus," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32431-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.