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Plus and minus ends of microtubules respond asymmetrically to kinesin binding by a long-range directionally driven allosteric mechanism
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Vu, Huong T., Zhang, Zhechun, Tehver, Riina and Thirumalai, D. (2022) Plus and minus ends of microtubules respond asymmetrically to kinesin binding by a long-range directionally driven allosteric mechanism. Science Advances, 8 (15). doi:10.1126/sciadv.abn0856 ISSN 2375-2548.
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Official URL: https://doi.org/10.1126/sciadv.abn0856
Abstract
Although it is known that majority of kinesin motors walk predominantly toward the plus end of microtubules (MTs) in a hand-over-hand manner, the structural origin of the stepping directionality is not understood. To resolve this issue, we modeled the structures of kinesin-1 (Kin1), MT, and the Kin1-MT complex using the elastic network model and calculated the residue-dependent responses to a local perturbation in the constructs. Kin1 binding elicits an asymmetric response that is pronounced in α/β-tubulin dimers in the plus end of the MT. Kin1 opens the clefts of multiple plus end α/β-tubulin dimers, creating binding-competent conformations, which is required for processivity. Reciprocally, MT induces correlations between switches I and II in the motor and enhances fluctuations in adenosine 5′-diphosphate and the residues in the binding pocket. Our findings explain both the directionality of stepping and MT effects on a key step in the catalytic cycle of kinesin.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||||
SWORD Depositor: | Library Publications Router | ||||||
Journal or Publication Title: | Science Advances | ||||||
Publisher: | American Association for the Advancement of Science (AAAS) | ||||||
ISSN: | 2375-2548 | ||||||
Official Date: | 15 April 2022 | ||||||
Dates: |
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Volume: | 8 | ||||||
Number: | 15 | ||||||
DOI: | 10.1126/sciadv.abn0856 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 14 November 2022 | ||||||
Date of first compliant Open Access: | 14 November 2022 |
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