Mapping interactions between myosin relay and converter domains that power muscle function.

Academic Article


  • Intramolecular communication within myosin is essential for its function as motor, but the specific amino acid residue interactions required are unexplored within muscle cells. Using Drosophila melanogaster skeletal muscle myosin, we performed a novel in vivo molecular suppression analysis to define the importance of three relay loop amino acid residues (Ile(508), Asn(509), and Asp(511)) in communicating with converter domain residue Arg(759). We found that the N509K relay mutation suppressed defects in myosin ATPase, in vitro motility, myofibril stability, and muscle function associated with the R759E converter mutation. Through molecular modeling, we define a mechanism for this interaction and suggest why the I508K and D511K relay mutations fail to suppress R759E. Interestingly, I508K disabled motor function and myofibril assembly, suggesting that productive relay-converter interaction is essential for both processes. We conclude that the putative relay-converter interaction mediated by myosin residues 509 and 759 is critical for the biochemical and biophysical function of skeletal muscle myosin and the normal ultrastructural and mechanical properties of muscle.
  • Authors

    Published In


  • ATPases, Drosophila, Electron Microscopy (EM), Myofibril, Myosin, Skeletal Muscle, Actins, Amino Acid Sequence, Animals, Animals, Genetically Modified, Biocatalysis, Calcium, Drosophila Proteins, Drosophila melanogaster, Female, Flight, Animal, Kinetics, Magnesium, Microscopy, Electron, Transmission, Models, Molecular, Molecular Sequence Data, Muscle, Skeletal, Mutation, Myofibrils, Myosins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Sarcomeres
  • Digital Object Identifier (doi)

    Author List

  • Kronert WA; Melkani GC; Melkani A; Bernstein SI
  • Start Page

  • 12779
  • End Page

  • 12790
  • Volume

  • 289
  • Issue

  • 18