Two recent articles 1,2 addressed the power-stroke of myosin VI molecules during stepping. Although both groups measured the angles of fluorescent probes attached on the myosin VI molecule lever arm using polarized fluorescence techniques, they differ about whether the myosin VI lever arm rotation is fixed 1 or variable 2 . Here we discuss the causes of the discrepancy between the two studies and the implications for myosin VI processive motility.Introduction: Myosin VI, an unconventional myosin motor that walks toward the minus ends of actin filaments, has received great attention recently. Reifenberger et al. 1 have presented evidence from Defocused Orientation and Positional Imaging (DOPI) assays that myosin VI lever arms tilt by an angle very close to 180° on each step. This contrasts with results from Sun et al. 2 wherein we applied single molecule Polarized Total Internal Reflection Fluorescence (polTIRF) microscopy and found variable degrees of tilting both in the axial and azimuthal directions relative to actin. This variability is consistent with the known variable step size of myosin VI. There are several technical differences in the two papers that interested researchers should understand, and more importantly, substantive differences in the conclusions.
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