Interhead distance measurements in myosin VI via SHRImP support a simplified hand-over-hand model

Biophys J. 2005 Jul;89(1):413-7. doi: 10.1529/biophysj.105.060608. Epub 2005 Apr 29.


Myosin VI walks in a hand-over-hand fashion with an average step size of 30 nm, which is much larger than its 10 nm lever arm. Recent experiments suggest that the myosin VI structure has an unfolded and flexible region in the proximal tail which makes such a large step possible. In addition, cryoelectron microscopy images of actomyosin VI show the two heads bound to the actin monomers with a broad distribution of distances, including some as close as a few nanometers. This observation, when combined with the existence of a flexible region in the structure, which takes part in stepping, challenged the hand-over-hand model. In the hand-over-hand model, the lever arm is considered to be rigid and the interhead separation should not be very different from 30 nm. We considered an alternative model in which myosin VI heads sequentially take 60 nm steps whereas the interhead separation alternates between a large and small value (x and 60 - x, where x < 30). To clarify these issues, we used a new technique, SHRImP, to measure the interhead distance of nearly rigor myosin VI molecules. Our data show a single peak at 29.3 +/- 0.7 nm, in agreement with the straightforward hand-over-hand model.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / chemistry
  • Actomyosin / chemistry*
  • Adenosine Triphosphate / chemistry
  • Animals
  • Biophysics / methods
  • Caenorhabditis elegans
  • Cryoelectron Microscopy
  • Dimerization
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / metabolism
  • Image Processing, Computer-Assisted
  • Models, Theoretical
  • Movement
  • Myosin Heavy Chains / chemistry*
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Software
  • Spectroscopy, Fourier Transform Infrared / instrumentation
  • Spectroscopy, Fourier Transform Infrared / methods
  • Statistics as Topic / methods*
  • Time Factors


  • Actins
  • myosin VI
  • Green Fluorescent Proteins
  • Adenosine Triphosphate
  • Actomyosin
  • Myosin Heavy Chains