Article

Human Myosin Vc Is a Low Duty Ratio Nonprocessive Motor

Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Journal of Biological Chemistry (Impact Factor: 4.57). 05/2008; 283(16):10581-92. DOI: 10.1074/jbc.M707657200
Source: PubMed

ABSTRACT There are three distinct members of the myosin V family in vertebrates, and each isoform is involved in different membrane
trafficking pathways. Both myosin Va and Vb have demonstrated that they are high duty ratio motors that are consistent with
the processive nature of these motors. Here we report that the ATPase cycle mechanism of the single-headed construct of myosin
Vc is quite different from those of other vertebrate myosin V isoforms. KATPase of the actin-activated ATPase was 62 μm, which is much higher than that of myosin Va (∼1 μm). The rate of ADP release from actomyosin Vc was 12.7 s-1, which was 2 times greater than the entire ATPase cycle rate, 6.5 s-1. Pi burst size was 0.31, indicating that the equilibrium of the ATP hydrolysis step is shifted to the prehydrolysis form. Our
kinetic model, based on all kinetic data we determined in this study, suggests that myosin Vc spends the majority of the ATPase
cycle time in the weak actin binding state in contrast to myosin Va and Vb. Consistently, the two-headed myosin Vc construct
did not show processive movement in total internal reflection fluorescence microscope analysis, demonstrating that myosin
Vc is a nonprocessive motor. Our findings suggest that myosin Vc fulfills its function as a cargo transporter by different
mechanisms from other myosin V isoforms.

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