Kinesin motility driven by subdomain dynamics
Abstract
The microtubule (MT)-associated motor protein kinesin utilizes its conserved ATPase head to achieve diverse motility characteristics. Despite considerable knowledge about how its ATPase activity and MT binding are coupled to the motility cycle, the atomic mechanism of the core events remain to be found. To obtain insights into the mechanism, we performed 38.5 microseconds of all-atom molecular dynamics simulations of kinesin-MT complexes in different nucleotide states. Local subdomain dynamics were found to be essential for nucleotide processing. Catalytic water molecules are dynamically organized by the switch domains of the nucleotide binding pocket while ATP is torsionally strained. Hydrolysis products are 'pulled' by switch-I, and a new ATP is "captured" by a concerted motion of the α0/L5/switch-I trio. The dynamic and wet kinesin-MT interface is tuned for rapid interactions while maintaining specificity. The resulting mechanism provides the flexibility necessary for walking in the crowded cellular environment.
Article and author information
Author details
Funding
National Institutes of Health (R01GM087677)
- Wonmuk Hwang
- Matthew Lang
PIttsburgh Supercomputing Center (Anton Supercomputer)
- Wonmuk Hwang
- Martin Karplus
Texas A&M Supercomputing Facility
- Wonmuk Hwang
Texas Advanced Computing Center
- Wonmuk Hwang
CHARMM Development Project
- Martin Karplus
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Antoine M van Oijen, University of Wollongong, Australia
Publication history
- Received: May 24, 2017
- Accepted: November 3, 2017
- Accepted Manuscript published: November 7, 2017 (version 1)
- Version of Record published: December 6, 2017 (version 2)
Copyright
© 2017, Hwang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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