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bioRxiv · 10.1101/2025.03.13.643154

Ndc80 complex, a conserved coupler for kinetochore-microtubule motility, is a sliding molecular clutch

Demidov, V.·Gonchar, I.·Tripathy, S. K.·Ataullakhanov, F. I.·Grishchuk, E.
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Abstract

Chromosome motion at spindle microtubule plus-ends relies on dynamic molecular bonds between kinetochores and proximal microtubule walls. Under opposing forces, kinetochores move bi-directionally along these walls while remaining near the ends, yet how continuous wall-sliding occurs without end-detachment remains unclear. Using ultrafast force-clamp spectroscopy, we show that single Ndc80 complexes, the primary microtubule-binding kinetochore component, exhibit processive, bi-directional sliding. Plus-end-directed forces induce a mobile catch-bond in Ndc80, increasing frictional resistance and restricting sliding toward the tip. Conversely, forces pulling Ndc80 away from the plus-end trigger mobile slip-bond behavior, facilitating sliding. This dual behavior arises from force-dependent modulation of the Nuf2 calponin-homology domains microtubule binding, identifying this subunit as a friction regulator. We propose that Ndc80cs ability to modulate sliding friction provides the mechanistic basis for the kinetochores end coupling, enabling its slip-clutch behavior. One Sentence SummaryDirection-dependent mobile catch- and slip-bond behavior of the microtubule-binding Ndc80 protein

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Demidov, V., Gonchar, I., Tripathy, S. K., Ataullakhanov, F. I., Grishchuk, E.. 2025-03-13. Ndc80 complex, a conserved coupler for kinetochore-microtubule motility, is a sliding molecular clutch. https://doi.org/10.1101/2025.03.13.643154

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