IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-53773-6.html
   My bibliography  Save this article

Cryo-EM structures of the membrane repair protein dysferlin

Author

Listed:
  • Hsiang-Ling Huang

    (The Ohio State University College of Medicine)

  • Giovanna Grandinetti

    (The Ohio State University College of Medicine
    The Ohio State University)

  • Sarah M. Heissler

    (The Ohio State University College of Medicine)

  • Krishna Chinthalapudi

    (The Ohio State University College of Medicine)

Abstract

Plasma membrane repair in response to damage is essential for cell viability. The ferlin family protein dysferlin plays a key role in Ca2+-dependent membrane repair in striated muscles. Mutations in dysferlin lead to a spectrum of diseases known as dysferlinopathies. The lack of a structure of dysferlin and other ferlin family members has impeded a mechanistic understanding of membrane repair mechanisms and the development of therapies. Here, we present the cryo-EM structures of the full-length human dysferlin monomer and homodimer at 2.96 Å and 4.65 Å resolution. These structures define the architecture of dysferlin, ferlin family-specific domains, and homodimerization mechanisms essential to function. Furthermore, biophysical and cell biology studies revealed how missense mutations in dysferlin contribute to disease mechanisms. In summary, our study provides a framework for the molecular mechanisms of dysferlin and the broader ferlin family, offering a foundation for the development of therapeutic strategies aimed at treating dysferlinopathies.

Suggested Citation

  • Hsiang-Ling Huang & Giovanna Grandinetti & Sarah M. Heissler & Krishna Chinthalapudi, 2024. "Cryo-EM structures of the membrane repair protein dysferlin," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53773-6
    DOI: 10.1038/s41467-024-53773-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-53773-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-53773-6?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. Yuemin Ma & Lei Ding & Zhenhai Li & Chun Zhou, 2023. "Structural basis for TRIM72 oligomerization during membrane damage repair," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Dimple Bansal & Katsuya Miyake & Steven S. Vogel & Séverine Groh & Chien-Chang Chen & Roger Williamson & Paul L. McNeil & Kevin P. Campbell, 2003. "Defective membrane repair in dysferlin-deficient muscular dystrophy," Nature, Nature, vol. 423(6936), pages 168-172, May.
    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. Mahtab Tavasoli & Sarah Lahire & Stanislav Sokolenko & Robyn Novorolsky & Sarah Anne Reid & Abir Lefsay & Meredith O. C. Otley & Kitipong Uaesoontrachoon & Joyce Rowsell & Sadish Srinivassane & Molly , 2022. "Mechanism of action and therapeutic route for a muscular dystrophy caused by a genetic defect in lipid metabolism," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Viviane Tran & Sarah Nahlé & Amélie Robert & Inès Desanlis & Ryan Killoran & Sophie Ehresmann & Marie-Pier Thibault & David Barford & Kodi S. Ravichandran & Martin Sauvageau & Matthew J. Smith & Marie, 2022. "Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration," Nature Communications, Nature, vol. 13(1), pages 1-15, 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:15:y:2024:i:1:d:10.1038_s41467-024-53773-6. 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.