The Relay/Converter Interface Influences Hydrolysis of ATP by Skeletal Muscle Myosin II.

Academic Article


  • The interface between relay and converter domain of muscle myosin is critical for optimal myosin performance. Using Drosophila melanogaster indirect flight muscle S1, we performed a kinetic analysis of the effect of mutations in the converter and relay domain. Introduction of a mutation (R759E) in the converter domain inhibits the steady-state ATPase of myosin S1, whereas an additional mutation in the relay domain (N509K) is able to restore the ATPase toward wild-type values. The R759E S1 construct showed little effect on most steps of the actomyosin ATPase cycle. The exception was a 25-30% reduction in the rate constant of the hydrolysis step, the step coupled to the cross-bridge recovery stroke that involves a change in conformation at the relay/converter domain interface. Significantly, the double mutant restored the hydrolysis step to values similar to the wild-type myosin. Modeling the relay/converter interface suggests a possible interaction between converter residue 759 and relay residue 509 in the actin-detached conformation, which is lost in R759E but is restored in N509K/R759E. This detailed kinetic analysis of Drosophila myosin carrying the R759E mutation shows that the interface between the relay loop and converter domain is important for fine-tuning myosin kinetics, in particular ATP binding and hydrolysis.
  • Authors

    Published In


  • actin, fluorescence, homology modeling, kinetics, muscle, myosin, protein structure-function, sequence alignment, Actins, Adenosine Triphosphatases, Adenosine Triphosphate, Animals, Drosophila Proteins, Drosophila melanogaster, Hydrolysis, Kinetics, Mutation, Missense, Protein Structure, Tertiary, Skeletal Muscle Myosins
  • Digital Object Identifier (doi)

    Author List

  • Bloemink MJ; Melkani GC; Bernstein SI; Geeves MA
  • Start Page

  • 1763
  • End Page

  • 1773
  • Volume

  • 291
  • Issue

  • 4