9QFD

Cryo-EM structure of the fully cofilin-1-decorated actin filament (cofilactin)

9QFD の概要

• エントリーDOI: 10.2210/pdb9qfd/pdb
• 関連するPDBエントリー: 9QF2
• EMDBエントリー: 53096 53106
• 分子名称: Actin, cytoplasmic 1, N-terminally processed, Cofilin-1, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: actin, cofilin, filament, cytoskeleton, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 14
• 化学式量合計: 424315.21

構造登録者

Oosterheert, W.,Boiero Sanders, M.,Hofnagel, O.,Bieling, P.,Raunser, S. (登録日: 2025-03-11, 公開日: 2025-10-08, 最終更新日: 2025-12-10)

主引用文献

Oosterheert, W.,Boiero Sanders, M.,Hofnagel, O.,Bieling, P.,Raunser, S.
Choreography of rapid actin filament disassembly by coronin, cofilin, and AIP1.
Cell, 188:6845-, 2025

PubMed Abstract: Rapid remodeling of actin filament (F-actin) networks is essential for the movement and morphogenesis of eukaryotic cells. The conserved actin-binding proteins coronin, cofilin, and actin-interacting protein 1 (AIP1) act in synergy to promote rapid F-actin network disassembly, but the underlying mechanisms have remained elusive. Here, using cryo-electron microscopy (cryo-EM), we uncover the concerted molecular actions of coronin, cofilin, and AIP1 that lead to actin filament aging and severing. We find that the cooperative binding of coronin allosterically promotes inorganic phosphate release from F-actin and induces filament undertwisting, thereby priming the filament for cofilin binding. Cofilin then displaces coronin from the filament via a strand-restricted cooperative binding mechanism. The resulting cofilactin serves as a high-affinity platform for AIP1, which induces severing by acting as a clamp that disrupts inter-subunit filament contacts. In this "molecular squeezing" mechanism, AIP1 and not cofilin is responsible for filament severing. Our work redefines the role of key disassembly factors in actin dynamics.

PubMed: 41075793
DOI: 10.1016/j.cell.2025.09.016

実験手法

ELECTRON MICROSCOPY (2.61 Å)