IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41579-x.html
   My bibliography  Save this article

Structural basis for calcium-stimulating pore formation of Vibrio α-hemolysin

Author

Listed:
  • Yu-Chuan Chiu

    (National Cheng Kung University)

  • Min-Chi Yeh

    (Academia Sinica)

  • Chun-Hsiung Wang

    (Academia Sinica)

  • Yu-An Chen

    (National Cheng Kung University)

  • Hsiang Chang

    (National Cheng Kung University)

  • Han-You Lin

    (National Taiwan University)

  • Meng-Chiao Ho

    (Academia Sinica
    National Taiwan University
    National Taiwan University)

  • Shih-Ming Lin

    (National Cheng Kung University
    National Cheng Kung University)

Abstract

Vibrio α-hemolysins (αHLs) are β-pore-forming toxins secreted by Vibrio pathogens, crucial for the facilitation of bacterial infections through host cell lysis. These toxins are produced as inactive precursors, requiring proteolytic maturation and membrane association for activation within host tissues. Here, we investigate Vibrio campbellii αHL (VcαHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC50 that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcαHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcαHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcαHL’s calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcαHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections.

Suggested Citation

  • Yu-Chuan Chiu & Min-Chi Yeh & Chun-Hsiung Wang & Yu-An Chen & Hsiang Chang & Han-You Lin & Meng-Chiao Ho & Shih-Ming Lin, 2023. "Structural basis for calcium-stimulating pore formation of Vibrio α-hemolysin," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41579-x
    DOI: 10.1038/s41467-023-41579-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41579-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41579-x?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. Nathan J. Hardenbrook & Shiheng Liu & Kang Zhou & Koyel Ghosal & Z. Hong Zhou & Bryan A. Krantz, 2020. "Atomic structures of anthrax toxin protective antigen channels bound to partially unfolded lethal and edema factors," Nature Communications, Nature, vol. 11(1), pages 1-10, 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.

      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:14:y:2023:i:1:d:10.1038_s41467-023-41579-x. 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.