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Microtubule end conversion mediated by motors and diffusing proteins with no intrinsic microtubule end-binding activity

Manas Chakraborty, Ekaterina V. Tarasovetc, Anatoly V. Zaytsev, Maxim Godzi, Ana C. Figueiredo, Fazly I. Ataullakhanov and Ekaterina L. Grishchuk ()
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Manas Chakraborty: University of Pennsylvania
Ekaterina V. Tarasovetc: University of Pennsylvania
Anatoly V. Zaytsev: University of Pennsylvania
Maxim Godzi: University of Pennsylvania
Ana C. Figueiredo: Universidade do Porto
Fazly I. Ataullakhanov: Russian Academy of Sciences
Ekaterina L. Grishchuk: University of Pennsylvania

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Accurate chromosome segregation relies on microtubule end conversion, the ill-understood ability of kinetochores to transit from lateral microtubule attachment to durable association with dynamic microtubule plus-ends. The molecular requirements for this conversion and the underlying biophysical mechanisms are elusive. We reconstituted end conversion in vitro using two kinetochore components: the plus end–directed kinesin CENP-E and microtubule-binding Ndc80 complex, combined on the surface of a microbead. The primary role of CENP-E is to ensure close proximity between Ndc80 complexes and the microtubule plus-end, whereas Ndc80 complexes provide lasting microtubule association by diffusing on the microtubule wall near its tip. Together, these proteins mediate robust plus-end coupling during several rounds of microtubule dynamics, in the absence of any specialized tip-binding or regulatory proteins. Using a Brownian dynamics model, we show that end conversion is an emergent property of multimolecular ensembles of microtubule wall-binding proteins with finely tuned force-dependent motility characteristics.

Date: 2019
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DOI: 10.1038/s41467-019-09411-7

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