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Structural analysis of a motor with increased mechanical output reveals new transitions in kinesin microtubule motility

English (英語)

Scientific Reports

16(1)

487

Nature Portfolio

2026-01-05

2026-01-14

Kinesin motors use ATP to produce force in cells, yet the conformational changes that generate force remain uncertain. Here, we report structural and mechanistic insights into a minus-end-directed kinesin-14 that exhibits increased mechanical output – the variant motor binds microtubules more tightly and moves with faster velocity than wild type. High-resolution structures, together with molecular dynamics simulations, reveal previously unobserved transitions in the nucleotide hydrolysis cycle. ADP release, triggered by microtubule binding, is coupled to twisting of the central β-sheet and stabilization of the stalk prior to the power stroke. ATP binding induces stalk fluctuations and a swing of the neck mimic, an element analogous to the kinesin-1 neck linker, resembling neck linker docking in plus-end-directed kinesins. The power stroke, characterized by a large stalk rotation, is followed by motor detachment from microtubules. The subsequent recovery stroke occurs while the motor is bound to ADP and free Pi, accompanied by β-strand-to-loop transitions, or β-sheet melting, implying that β-sheet refolding facilitates Pi release. The observed twisting and melting identify the central β-sheet as the long-sought elastic element or spring required for motor force production. The transitions we observe in kinesin-14 may also apply to other kinesins – this remains to be tested.

Motor spring-like element

学術雑誌論文

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