PT  - JOURNAL ARTICLE
AU  - Manas Chakraborty
AU  - Ekaterina Tarasovetc
AU  - Anatoly V. Zaytsev
AU  - Maxim Godzi
AU  - Ana C. Figueiredo
AU  - Fazly I. Ataullakhanov
AU  - Ekaterina L. Grishchuk
TI  - Molecular requirements for transition from lateral to end-on microtubule binding and dynamic coupling
AID  - 10.1101/481713
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 481713
4099  - http://biorxiv.org/content/early/2018/11/29/481713.short
4100  - http://biorxiv.org/content/early/2018/11/29/481713.full
AB  - 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 ill-understood. 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.AbbreviationsMAPmicrotubule associated proteinMTmicrotubuleMSDmean squared displacementTIRFtotal internal reflection fluorescence