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| Title | Cryo-EM structures of the membrane repair protein dysferlin. |
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| Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 9650, Year 2024 |
| Publish date | Nov 7, 2024 |
 Authors | Hsiang-Ling Huang / Giovanna Grandinetti / Sarah M Heissler / Krishna Chinthalapudi /  |
| PubMed Abstract | Plasma membrane repair in response to damage is essential for cell viability. The ferlin family protein dysferlin plays a key role in Ca-dependent membrane repair in striated muscles. Mutations in ...Plasma membrane repair in response to damage is essential for cell viability. The ferlin family protein dysferlin plays a key role in Ca-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. |
 External links | Nat Commun / PubMed:39511170 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.96 - 4.65 Å |
| Structure data | EMDB-44348, PDB-9b8k: EMDB-44349, PDB-9b8l: |
| Source |
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 Keywords | MEMBRANE PROTEIN / Single-pass type II membrane protein / membrane repair / calcium ion sensor |
homo sapiens (human)