9L7M

Nucleotide-free kinesin-1 motor domain bound to the microtubule

9L7M の概要

• エントリーDOI: 10.2210/pdb9l7m/pdb
• 関連するPDBエントリー: 9L6K 9L78 9L7E
• EMDBエントリー: 62874
• 分子名称: Tubulin alpha-1B chain, Tubulin beta chain, Kinesin-1 heavy chain, ... (5 entities in total)
• 機能のキーワード: kinesin, microtubule, motor protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 242677.76

構造登録者

Makino, T.,Komori, Y.,Yanagisawa, H.,Tomishige, M.,Kikkawa, M. (登録日: 2024-12-26, 公開日: 2025-04-23, 最終更新日: 2025-05-21)

主引用文献

Makino, T.,Kanada, R.,Mori, T.,Miyazono, K.I.,Komori, Y.,Yanagisawa, H.,Takada, S.,Tanokura, M.,Kikkawa, M.,Tomishige, M.
Tension-induced suppression of allosteric conformational changes coordinates kinesin-1 stepping.
J.Cell Biol., 224:-, 2025

PubMed Abstract: Kinesin-1 walks along microtubules by alternating ATP hydrolysis and movement of its two motor domains ("head"). The detached head preferentially binds to the forward tubulin-binding site after ATP binds to the microtubule-bound head, but the mechanism preventing premature microtubule binding while the partner head awaits ATP remains unknown. Here, we examined the role of the neck linker, the segment connecting two heads, in this mechanism. Structural analyses of the nucleotide-free head revealed a bulge just ahead of the neck linker's base, creating an asymmetric constraint on its mobility. While the neck linker can stretch freely backward, it must navigate around this bulge to extend forward. We hypothesized that increased neck linker tension suppresses premature binding of the tethered head, which was supported by molecular dynamics simulations and single-molecule fluorescence assays. These findings demonstrate a tension-dependent allosteric mechanism that coordinates the movement of two heads, where neck linker tension modulates the allosteric conformational changes rather than directly affecting the nucleotide state.

PubMed: 40298806
DOI: 10.1083/jcb.202501253

実験手法

ELECTRON MICROSCOPY (3.48 Å)