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Backstepping mechanism of kinesin-1

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Toleikis, Algirdas, Carter, Nicholas J. and Cross, Robert A. (2020) Backstepping mechanism of kinesin-1. Biophysical Journal, 119 (10). pp. 1984-1994. doi:10.1016/j.bpj.2020.09.034 ISSN 0006-3495.

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Official URL: http://dx.doi.org/10.1016/j.bpj.2020.09.034

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Abstract

Kinesin-1 is an ATP-driven molecular motor that transports cellular cargo along microtubules. At low loads, kinesin-1 almost always steps forward, toward microtubule plus ends, but at higher loads, it can also step backward. Backsteps are usually 8 nm but can be larger. These larger backward events of 16 nm, 24 nm, or more are thought to be slips rather than steps because they are too fast to consist of multiple, tightly coupled 8-nm steps. Here, we propose that not only these larger backsteps, but all kinesin-1 backsteps, are slips. We show first that kinesin waits before forward steps for less time than before backsteps and detachments; second, we show that kinesin waits for the same amount of time before backsteps and detachments; and third, we show that by varying the microtubule type, we can change the ratio of backsteps to detachments without affecting forward stepping. Our findings indicate that backsteps and detachments originate from the same state and that this state arises later in the mechanochemical cycle than the state that gives rise to forward steps. To explain our data, we propose that, in each cycle of ATP turnover, forward kinesin steps can only occur before Pi release, whereas backslips and detachments can only occur after Pi release. In the scheme we propose, Pi release gates access to a weak binding K⋅ADP-K⋅ADP state that can slip back along the microtubule, re-engage, release ADP, and try again to take an ATP-driven forward step. We predict that this rescued detachment pathway is key to maintaining kinesin processivity under load.

Item Type: Journal Article
Subjects: Q Science > QH Natural history
Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Kinesin , Kinesin -- Movements, Microtubules , Adenosine triphosphatase
Journal or Publication Title: Biophysical Journal
Publisher: Elsevier
ISSN: 0006-3495
Official Date: 17 November 2020
Dates:
DateEvent
17 November 2020Published
5 October 2020Available
16 September 2020Accepted
Volume: 119
Number: 10
Page Range: pp. 1984-1994
DOI: 10.1016/j.bpj.2020.09.034
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Copyright Holders: © 2020 Biophysical Society
Date of first compliant deposit: 22 December 2020
Date of first compliant Open Access: 5 January 2021
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
103895/Z/14/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
Is Part Of: 1

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