8VO7

Cryo-EM structure of fascin crosslinked F-actin

8VO7 の概要

• エントリーDOI: 10.2210/pdb8vo7/pdb
• EMDBエントリー: 43366
• 分子名称: Fascin, Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: cytoskeleton, f-actin crosslinker, f-actin bundle, structural protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 307510.94

構造登録者

Gong, R.,Reynolds, M.J.,Alushin, G.M. (登録日: 2024-01-14, 公開日: 2025-01-15, 最終更新日: 2025-02-05)

主引用文献

Gong, R.,Reynolds, M.J.,Carney, K.R.,Hamilton, K.,Bidone, T.C.,Alushin, G.M.
Fascin structural plasticity mediates flexible actin bundle construction.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Fascin cross-links actin filaments (F-actin) into bundles that support tubular membrane protrusions including filopodia and stereocilia. Fascin dysregulation drives aberrant cell migration during metastasis, and fascin inhibitors are under development as cancer therapeutics. Here, we use cryo-EM, cryo-electron tomography coupled with custom denoising and computational modeling to probe human fascin-1's F-actin cross-linking mechanisms across spatial scales. Our fascin cross-bridge structure reveals an asymmetric F-actin binding conformation that is allosterically blocked by the inhibitor G2. Reconstructions of seven-filament hexagonal bundle elements, variability analysis and simulations show how structural plasticity enables fascin to bridge varied interfilament orientations, accommodating mismatches between F-actin's helical symmetry and bundle hexagonal packing. Tomography of many-filament bundles and modeling uncover geometric rules underlying emergent fascin binding patterns, as well as the accumulation of unfavorable cross-links that limit bundle size. Collectively, this work shows how fascin harnesses fine-tuned nanoscale structural dynamics to build and regulate micron-scale F-actin bundles.

PubMed: 39833469
DOI: 10.1038/s41594-024-01477-2

実験手法

ELECTRON MICROSCOPY (3.1 Å)