Structural Insight Into the UNC-45-myosin Complex

Proteins. 2013 Jul;81(7):1212-21. doi: 10.1002/prot.24270. Epub 2013 Apr 10.

Abstract

The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45-myosin complex using various in silico methods. Initially, the human UNC-45B binding epitope was identified and the protein was docked to the cardiac myosin (MYH7) motor domain. The final UNC45B-MYH7 structure was obtained by performing of total 630 ns molecular dynamics simulations. The results indicate a complex formation, which is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosin-actin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15-16 hypertrophic cardiomyopathy mutations and provide directions for drug targeting.

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Molecular Chaperones / chemistry
  • Molecular Dynamics Simulation*
  • Multiprotein Complexes / chemistry*
  • Myosins / chemistry*
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Multiprotein Complexes
  • UNC45A protein, human
  • Myosins