7SXA

T-Plastin-F-actin complex, pre-bundling intermediate state

7SXA の概要

• エントリーDOI: 10.2210/pdb7sxa/pdb
• EMDBエントリー: 24323 25494 25495 25496
• 分子名称: Plastin-3, Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: t-plastin, plastin, actin, filopodium, cytoskeleton, cell protrusion, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 198581.30

構造登録者

Mei, L.,Reynolds, M.J.,Alushin, G.M. (登録日: 2021-11-22, 公開日: 2022-08-31, 最終更新日: 2026-03-04)

主引用文献

Mei, L.,Reynolds, M.J.,Garbett, D.,Gong, R.,Meyer, T.,Alushin, G.M.
Structural mechanism for bidirectional actin cross-linking by T-plastin.
Proc.Natl.Acad.Sci.USA, 119:e2205370119-e2205370119, 2022

PubMed Abstract: To orchestrate cell mechanics, trafficking, and motility, cytoskeletal filaments must assemble into higher-order networks whose local subcellular architecture and composition specify their functions. Cross-linking proteins bridge filaments at the nanoscale to control a network's μm-scale geometry, thereby conferring its mechanical properties and functional dynamics. While these interfilament linkages are key determinants of cytoskeletal function, their structural mechanisms remain poorly understood. Plastins/fimbrins are an evolutionarily ancient family of tandem calponin-homology domain (CHD) proteins required to construct multiple classes of actin networks, which feature diverse geometries specialized to power cytokinesis, microvilli and stereocilia biogenesis, and persistent cell migration. Here, we focus on the structural basis of actin network assembly by human T-plastin, a ubiquitously expressed isoform necessary for the maintenance of stable cellular protrusions generated by actin polymerization forces. By implementing a machine-learning-enabled cryo-electron microscopy pipeline for visualizing cross-linkers bridging multiple filaments, we uncover a sequential bundling mechanism enabling T-plastin to bridge pairs of actin filaments in both parallel and antiparallel orientations. T-plastin populates distinct structural landscapes in these two bridging orientations that are selectively compatible with actin networks featuring divergent architectures and functions. Our structural, biochemical, and cell biological data highlight inter-CHD linkers as key structural elements underlying flexible but stable cross-linking that are likely to be disrupted by T-plastin mutations that cause hereditary bone diseases.

PubMed: 36067297
DOI: 10.1073/pnas.2205370119

実験手法

ELECTRON MICROSCOPY (6.87 Å)