Dynamic modulation of the regulatory domain of myosin heads by pH, ionic strength, and RLC phosphorylation in synthetic myosin filaments

Biochemistry. 1999 Mar 9;38(10):3127-32. doi: 10.1021/bi982553g.

Abstract

The position of the myosin head with respect to the filament backbone is thought to be a function of pH, ionic strength (micro) and the extent of regulatory light chain (RLC) phosphorylation [Harrington (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 5066-5070]. The object of this study is to examine the dynamics of the proximal part of the myosin head (regulatory domain) which accompany the changes in head disposition. The essential light chain was labeled at Cys177 with the indanedione spin-label followed by the exchange of the labeled proteins into myosin. The mobility of the labeled domain was investigated with saturation transfer electron paramagnetic resonance in reconstituted, synthetic myosin filaments. We have found that the release of the heads from the myosin filament surface by reduction of electrostatic charge is accompanied by a 2-fold increase in the mobility of the regulatory domain. Phosphorylation of the RLC by myosin light chain kinase resulted in a smaller 1. 5-fold increase of motion, establishing that the head disordering observed by electron microscopy [Levine et al. (1996) Biophys. J. 71, 898-907] is due to increased mobility of the heads. This result indirectly supports the hypothesis that the RLC phosphorylation effect on potentiation of force arises from a release of heads from the filament surface and a shift of the heads toward actin.

Publication types

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

MeSH terms

  • Animals
  • Hydrogen-Ion Concentration
  • Myosin Light Chains / chemistry*
  • Myosin Light Chains / metabolism*
  • Myosin Subfragments / chemistry*
  • Myosin Subfragments / metabolism*
  • Myosins / chemical synthesis
  • Osmolar Concentration
  • Phosphorylation
  • Protein Structure, Tertiary
  • Rabbits
  • Spin Labels
  • Thermodynamics

Substances

  • Myosin Light Chains
  • Myosin Subfragments
  • Spin Labels
  • Myosins