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

• Autor(es): Chakraborty, M ; Tarasovetc, EV ; Zaytsev, AV ; Godzi, M ; Figueiredo, AC ; Ataullakhanov, FI ; Grishchuk, EL
• Data: 2019
• Identificador Persistente: https://hdl.handle.net/10216/136301
• Origem: Repositório Aberto da Universidade do Porto
• Tipo de Documento: Artigo científico
• Idioma: Inglês

Descrição

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.