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

Chromosome motion at spindle microtubule plus ends relies on dynamic molecular bonds between kinetochores and proximal microtubule walls. Under opposing forces, kinetochores move bidirectionally 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, bidirectional 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 domain's microtubule binding, identifying this subunit as a friction regulator. We propose that Ndc80's ability to modulate sliding friction provides the mechanistic basis for the kinetochore's end coupling, enabling its slip-clutch behavior.

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Publication Details

Journal
Science Advances
Published
2025-09-03
DOI
https://doi.org/10.1126/sciadv.adx0005
Citations
1
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
1.15
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article

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

Suvranta K. Tripathy, Ivan V. Gonchar, Ekaterina L. Grishchuk, Vladimir Demidov et al.
1 citations
Science Advances
Microtubule and mitosis dynamics
1.15
article

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

Suvranta K. Tripathy, Ivan V. Gonchar, Ekaterina L. Grishchuk, Vladimir Demidov, Фазоил И. Атауллаханов
article en
1 citations

Abstract

Chromosome motion at spindle microtubule plus ends relies on dynamic molecular bonds between kinetochores and proximal microtubule walls. Under opposing forces, kinetochores move bidirectionally 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, bidirectional 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 domain's microtubule binding, identifying this subunit as a friction regulator. We propose that Ndc80's ability to modulate sliding friction provides the mechanistic basis for the kinetochore's end coupling, enabling its slip-clutch behavior.

Science AdvancesVol. 11(36)
University of Pennsylvania (US)
Openalex Percentile: Top 20%
Microtubule and mitosis dynamics
1.15
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Ndc80 complex, a conserved coupler for kinetochore-microtubule motility, is a sliding molecular clutch — Suvranta K. Tripathy, Ivan V. Gonchar, et al. · Science Advances (2025) | TGRS Research Map | TGRS