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 remodeling 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 across the observed functional states. In contrast, the N-

SUBMITTER: Constantin Cretu 

PROVIDER: S-SCDT-10_1038-S44318-025-00463-8 | biostudies-other |

REPOSITORIES: biostudies-other