title: Structural insight into the UNC-45-myosin complex.
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.
authors: Micar 21 Ltd., 1470 Sofia, Bulgaria. fratev@clbme.bas.bg
authors: Filip
authors: F
authors: Fratev
authors: Svava
authors: S
authors: Osk Jónsdóttir
authors: Ilza
authors: I
authors: Pajeva
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D046912:Multiprotein Complexes / Q000737:chemistry*; D009218:Myosins / Q000737:chemistry*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C509158:UNC45A protein, human; D009218:Myosins