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-Structure paper
| タイトル | Choreography of rapid actin filament disassembly by coronin, cofilin, and AIP1. |
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| ジャーナル・号・ページ | Cell, Vol. 188, Issue 24, Page 6845-6860.e27, Year 2025 |
| 掲載日 | 2025年11月26日 |
著者 | Wout Oosterheert / Micaela Boiero Sanders / Oliver Hofnagel / Peter Bieling / Stefan Raunser / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Cell / PubMed:41075793 |
| 手法 | EM (単粒子) / EM (らせん対称) |
| 解像度 | 2.18 - 4.62 Å |
| 構造データ | EMDB-53093, PDB-9qew: EMDB-53094, PDB-9qey: EMDB-53096, PDB-9qf2: EMDB-53105, PDB-9qfb: EMDB-53106, PDB-9qfd: EMDB-53107, PDB-9qfe: EMDB-53108, PDB-9qfg: EMDB-53110, PDB-9qfj: ![]() EMDB-53111: Cryo-EM reconstruction of the Coronin-1B-decorated actin filament bound by two Cofilin-1 molecules (crosslinked) ![]() EMDB-53112: Cryo-EM reconstruction of the Coronin-1B-decorated actin filament bound by three Cofilin-1 molecules (crosslinked) ![]() EMDB-53113: Cryo-EM reconstruction of the Coronin-1B-decorated actin filament bound by four Cofilin-1 molecules (crosslinked) EMDB-53114, PDB-9qfk: ![]() EMDB-53118: Cryo-EM reconstruction of the cofilactin filament core bound by AIP1 EMDB-53119, PDB-9qfo: EMDB-53121, PDB-9qfq: EMDB-53122, PDB-9qfw: |
| 化合物 | ![]() ChemComp-ADP: ![]() ChemComp-MG: ![]() ChemComp-PO4: ![]() ChemComp-HOH: |
| 由来 |
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キーワード | STRUCTURAL PROTEIN / actin / filament / cytoskeleton / coronin / cofilin / pointed end / AIP1 / barbed end |
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