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Friday, September 5, 2014

Tension on the linker gates the ​ATP-dependent release of ​dynein from microtubules

Frank B. Cleary, Mark A. Dewitt, Thomas Bilyard, Zaw Min Htet, Vladislav Belyy, Danna D. Chan, Amy Y. Chang & Ahmet Yildiz

Cytoplasmic ​dynein is a dimeric motor that transports intracellular cargoes towards the minus end of microtubules (MTs). In contrast to other processive motors, stepping of the ​dynein motor domains (heads) is not precisely coordinated. Therefore, the mechanism of ​dynein processivity remains unclear. Here, by engineering the mechanical and catalytic properties of the motor, we show that ​dynein processivity minimally requires a single active head and a second inert MT-binding domain. Processivity arises from a high ratio of MT-bound to unbound time, and not from interhead communication. In addition, nucleotide-dependent microtubule release is gated by tension on the linker domain. Intramolecular tension sensing is observed in ​dynein’s stepping motion at high interhead separations. On the basis of these results, we propose a quantitative model for the stepping characteristics of ​dynein and its response to chemical and mechanical perturbation.

DOI

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