9B8L

Cryo-EM structure of human dysferlin dimer

これはPDB形式変換不可エントリーです。

9B8L の概要

• エントリーDOI: 10.2210/pdb9b8l/pdb
• EMDBエントリー: 44349
• 分子名称: Dysferlin (1 entity in total)
• 機能のキーワード: single-pass type ii membrane protein, membrane repair, calcium ion sensor, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 475154.19

構造登録者

Huang, H.L.,Heissler, S.M.,Chinthalapudi, K. (登録日: 2024-03-30, 公開日: 2024-11-27)

主引用文献

Huang, H.L.,Grandinetti, G.,Heissler, S.M.,Chinthalapudi, K.
Cryo-EM structures of the membrane repair protein dysferlin.
Nat Commun, 15:9650-9650, 2024

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 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.

PubMed: 39511170
DOI: 10.1038/s41467-024-53773-6

実験手法

ELECTRON MICROSCOPY (4.65 Å)