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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
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 | ||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology |
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| 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: |
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| 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: |
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| Is Part Of: | 1 |
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