9QLN
Human myoferlin (1-1997) in the lipid-free, Ca2+-bound state
This is a non-PDB format compatible entry.
Summary for 9QLN
| Entry DOI | 10.2210/pdb9qln/pdb |
| Related | 9H6X 9QKV 9QLE 9QLF |
| EMDB information | 53229 |
| Descriptor | Myoferlin, CALCIUM ION (2 entities in total) |
| Functional Keywords | ferlins, myoferlin, multi-c2 domain, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 232866.42 |
| Authors | |
| Primary citation | Cretu, C.,Chernev, A.,Kibedi Szabo, C.Z.,Pena, V.,Urlaub, H.,Moser, T.,Preobraschenski, J. Structural insights into lipid membrane binding by human ferlins. Embo J., 2025 Cited by PubMed Abstract: Ferlins are ancient membrane proteins with a unique architecture, and play central roles in crucial processes that involve Ca-dependent vesicle fusion. Despite their links to multiple human diseases and numerous functional studies, a mechanistic understanding of how these multi-C 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 Ca- 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 CC-CD region, is rigid and exhibits only little variability across the observed functional states. In contrast, the N-terminal CB and the C-terminal CF-CG domains cycle between alternative conformations and, in response to Ca, close the ferlin ring, promoting tight interaction with the target membrane. Probing key domain interfaces validates the observed architecture, and informs a model of how ferlins engage lipid bilayers in a Ca-dependent manner. This work reveals the general principles of human ferlin structures and provides a framework for future analyses of ferlin-dependent cellular functions and disease mechanisms. PubMed: 40437073DOI: 10.1038/s44318-025-00463-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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