9QLE

Human myoferlin (1-1997) in complex with an MSP2N2 lipid nanodisc (15 mol% DOPS, 2 mol% PI(4,5)P2)

これはPDB形式変換不可エントリーです。

9QLE の概要

• エントリーDOI: 10.2210/pdb9qle/pdb
• 関連するPDBエントリー: 9H6X 9QKV
• EMDBエントリー: 51902 53222 53225
• 分子名称: Myoferlin, 1,2-DICAPROYL-SN-PHOSPHATIDYL-L-SERINE, CALCIUM ION (3 entities in total)
• 機能のキーワード: ferlins, myoferlin, multi-c2 domains, lipid nanodisc, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 233937.61

構造登録者

Cretu, C.,Moser, T. (登録日: 2025-03-20, 公開日: 2025-06-04, 最終更新日: 2025-07-23)

主引用文献

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., 44:3926-3958, 2025

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: 40437073
DOI: 10.1038/s44318-025-00463-8

実験手法

ELECTRON MICROSCOPY (2.8 Å)