Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase.

Academic Article


  • UNC-45 belongs to the UCS (UNC-45, CRO1, She4p) domain protein family, whose members interact with various classes of myosin. Here we provide structural and biochemical evidence that Escherichia coli-expressed Drosophila UNC-45 (DUNC-45) maintains the integrity of several substrates during heat-induced stress in vitro. DUNC-45 displays chaperone function in suppressing aggregation of the muscle myosin heavy meromyosin fragment, the myosin S-1 motor domain, alpha-lactalbumin and citrate synthase. Biochemical evidence is supported by electron microscopy, which reveals the first structural evidence that DUNC-45 prevents inter- or intra-molecular aggregates of skeletal muscle heavy meromyosin caused by elevated temperatures. We also demonstrate for the first time that UNC-45 is able to refold a denatured substrate, urea-unfolded citrate synthase. Overall, this in vitro study provides insight into the fate of muscle myosin under stress conditions and suggests that UNC-45 protects and maintains the contractile machinery during in vivo stress.
  • Authors


  • Animals, Citrate (si)-Synthase, Drosophila Proteins, Drosophila melanogaster, Escherichia coli, Heat-Shock Response, Lactalbumin, Molecular Chaperones, Muscle Contraction, Myosin Subfragments, Protein Folding, Skeletal Muscle Myosins
  • Digital Object Identifier (doi)

    Pubmed Id

  • 21071040
  • Author List

  • Melkani GC; Lee CF; Cammarato A; Bernstein SI
  • Start Page

  • 317
  • End Page

  • 322
  • Volume

  • 396
  • Issue

  • 2