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.
Ndc80 complex, a conserved coupler for kinetochore-microtubule motility, is a sliding molecular clutch.
Ndc80 复合物是动粒-微管运动的保守耦合器,是一种滑动分子离合器
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作者:Demidov Vladimir M, Gonchar Ivan V, Tripathy Suvranta K, Ataullakhanov Fazly I, Grishchuk Ekaterina L
| 期刊: | Science Advances | 影响因子: | 12.500 |
| 时间: | 2025 | 起止号: | 2025 Sep 5; 11(36):eadx0005 |
| doi: | 10.1126/sciadv.adx0005 | 研究方向: | 其它 |
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