Structural insights into lipid membrane binding by human ferlins.

ABSTRACT: Ferlins are ancient membrane proteins with a unique architecture, and play central roles in crucial processes that involve Ca²⁺-dependent vesicle fusion. Despite their links to multiple human diseases and numerous functional studies, a mechanistic understanding of how these multi-C₂ domain-containing proteins interact with lipid membranes to promote membrane remodelling and fusion is currently lacking. Here we obtain near-complete cryo-electron microscopy structures of human myoferlin and dysferlin in their Ca²⁺- and lipid-bound states. We show that ferlins adopt compact, ring-like tertiary structures upon membrane binding. The top arch of the ferlin ring, composed of the C₂C-C₂D region, is rigid and exhibits only little variability ac

SUBMITTER: Cretu C 

PROVIDER: S-EPMC12264198 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature