Ionic interactions play a role in the regulatory mechanism of scallop heavy meromyosin

Biophys J. 2003 Aug;85(2):1053-62. doi: 10.1016/S0006-3495(03)74544-5.

Abstract

Heavy meromyosin from scallop (scHMM) striated muscle is regulated by calcium binding to the essential light chain. The regulation can be modeled with a calcium-dependent equilibrium between on and off scHMM conformations. The observed rate constant for mant-ADP dissociation from scHMM is calcium dependent, and we show here that it can be used to define the equilibrium constant (K(eq)) between on and off conformations. The data show that K(eq) is markedly ionic strength dependent, with high salt (>/=200 mM) abolishing the off state even in the absence of calcium and low salt (<50 mM) favoring the off state even in the presence of calcium. Debye-Huckel plots of the equilibrium constant (K(eq)) for the on and off forms gave parallel slopes (5.94 +/- 0.33 and 6.36 +/- 0.17 M(-0.5)) in the presence and absence of calcium. The presence of an equilibrium mixture of two conformations was confirmed by sedimentation data and the effects of ADP, calcium and ionic strength were in qualitative agreement. Thus scHMM exists in two conformations that can be distinguished in sedimentation profiles and by the rate of release of mant-ADP. Increasing salt concentrations biases the system toward the on state, suggesting a role for ionic interactions in stabilizing the off state.

Publication types

  • Comparative Study
  • Evaluation Study
  • 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.
  • Validation Study

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives*
  • Adenosine Diphosphate / chemistry*
  • Animals
  • Calcium / chemistry*
  • Computer Simulation
  • Fractionation, Field Flow
  • Ions / chemistry
  • Kinetics
  • Models, Chemical*
  • Molecular Motor Proteins / chemistry*
  • Mollusca / chemistry*
  • Muscle, Skeletal / chemistry*
  • Myosin Subfragments / chemistry*
  • Potassium Chloride / chemistry*
  • Protein Binding
  • Protein Conformation
  • Structure-Activity Relationship
  • ortho-Aminobenzoates / chemistry*

Substances

  • Ions
  • Molecular Motor Proteins
  • Myosin Subfragments
  • ortho-Aminobenzoates
  • Adenosine Diphosphate
  • Potassium Chloride
  • 3'-O-(N-methylanthraniloyl)adenosine 5'-diphosphate
  • Calcium