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Published Online December 4, 2003
Science DOI: 10.1126/science.1092985

Reports

Submitted on September 27, 2003
Accepted on November 25, 2003

Kinesin Moves by an Asymmetric Hand-Over-Hand Mechanism

Charles L. Asbury 1, Adrian N. Fehr 2, Steven M. Block 3*

1 Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
2 Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
3 Department of Biological Sciences, Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.

* To whom correspondence should be addressed. E-mail: sblock{at}stanford.edu.

Kinesin is a double-headed motor protein that moves along microtubules in 8-nm steps. Two broad classes of model have been invoked to explain kinesin movement: hand-over-hand and inchworm. In hand-over-hand models, the heads exchange leading and trailing roles with every step, whereas no such exchange is postulated for inchworm models, where one head always leads. By measuring the stepwise motion of individual enzymes, we find that some kinesin molecules exhibit a striking alternation in the dwell times between sequential steps, causing these motors to "limp" along the microtubule. Limping implies that kinesin molecules strictly alternate between two different conformations as they step, indicative of an asymmetric, hand-over-hand mechanism.


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