Grant, Barry J., Gheorghe, Dana M., Zheng, Wenjun, Alonso, M. (Maria), Huber, Gary, Dlugosz, Maciej, McCammon, J. Andrew and Cross, R. A.. (2011) Electrostatically biased binding of kinesin to microtubules. PLoS Biology, Vol.9 (No.11). e1001207. ISSN 1545-7885

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Abstract

The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Kinesin -- Movements
Journal or Publication Title:	PLoS Biology
Publisher:	Public Library of Science
ISSN:	1545-7885
Date:	November 2011
Volume:	Vol.9
Number:	No.11
Page Range:	e1001207
Identification Number:	10.1371/journal.pbio.1001207
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
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URI:	http://wrap.warwick.ac.uk/id/eprint/40144

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