9KBX

CryoEM structure of F-actin bound with GAS2-CH3 domain.

9KBX の概要

• エントリーDOI: 10.2210/pdb9kbx/pdb
• EMDBエントリー: 62233
• 分子名称: Growth arrest-specific protein 2, Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: cytoskeleton, structural protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 204408.14

構造登録者

An, J.,Imasaki, T.,Narita, A.,Niwa, S.,Sasaki, R.,Makino, T.,Nitta, R.,Kikkawa, M. (登録日: 2024-10-31, 公開日: 2025-09-10)

主引用文献

An, J.,Imasaki, T.,Narita, A.,Niwa, S.,Sasaki, R.,Makino, T.,Nitta, R.,Kikkawa, M.
Dimerization of GAS2 mediates crosslinking of microtubules and F-actin.
Embo J., 44:2997-3024, 2025

PubMed Abstract: The spectraplakin family protein GAS2 was originally identified as a growth arrest-specific protein, and recent studies have revealed its involvement in multiple cellular processes. Its dual interaction with actin filaments and microtubules highlights its essential role in cytoskeletal organization, such as cell division, apoptosis, and possibly tumorigenesis. However, the structural basis of cytoskeletal dynamics regulation by GAS2 remains unclear. In this study, we present cryo-electron microscopy structures of the GAS2 type 3 calponin homology domain (CH3) in complex with F-actin at 2.8 Å resolution, thus solving the first type CH3 domain structure bound to F-actin and confirming its actin-binding activity. We also provide the first near-atomic resolution cryo-EM structure of the GAS2-GAR domain bound to microtubules and identify conserved microtubule-binding residues. Our biochemical experiments show that GAS2 promotes microtubule nucleation and polymerization, and that its C-terminal region is essential for dimerization, bundling of both F-actin and microtubules, and microtubule nucleation. As mutations leading to expression of C-terminally truncated GAS2 have been linked to hearing loss, these findings suggest that the disruption of GAS2-dependent cytoskeletal organisation could underlie auditory dysfunction.

PubMed: 40169809
DOI: 10.1038/s44318-025-00415-2

実験手法

ELECTRON MICROSCOPY (2.8 Å)