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Curr Biol. 2015 May 4;25(9):1166-75. doi: 10.1016/j.cub.2015.03.013. Epub 2015 Apr 9.

The Mechanochemical Cycle of Mammalian Kinesin-2 KIF3A/B under Load.

Author information

1
Department of Physics, Stanford University, Stanford, CA 94305, USA.
2
Department of Bioengineering, Pennsylvania State University, University Park, PA 16802, USA.
3
Department of Biology, Stanford University, Stanford, CA 94305, USA; Department of Applied Physics, Stanford University, Stanford, CA 94305, USA. Electronic address: sblock@stanford.edu.

Abstract

The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.

PMID:
25866395
PMCID:
PMC4422762
DOI:
10.1016/j.cub.2015.03.013
[Indexed for MEDLINE]
Free PMC Article

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