title: The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.
abstract: The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding and assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural and biochemical data demonstrate that UNC-45 forms linear protein chains that offer multiple binding sites for cooperating chaperones and client proteins. Accordingly, Hsp70 and Hsp90, which bind to the TPR domain of UNC-45, could act in concert and with defined periodicity on captured myosin molecules. In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. In fact, expression of transgenes blocking UNC-45 chain formation induces dominant-negative defects in the sarcomere structure and function of wild-type worms. Together, these findings uncover a filament assembly factor that directly couples myosin folding with myofilament formation.
authors: Research Institute of Molecular Pathology, Dr. Bohrgasse 7, 1030 Vienna, Austria.
authors: Linn
authors: L
authors: Gazda
authors: Wojciech
authors: W
authors: Pokrzywa
authors: Doris
authors: D
authors: Hellerschmied
authors: Thomas
authors: T
authors: Löwe
authors: Ignasi
authors: I
authors: Forné
authors: Felix
authors: F
authors: Mueller-Planitz
authors: Thorsten
authors: T
authors: Hoppe
authors: Tim
authors: T
authors: Clausen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009210:Myofibrils / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012518:Sarcomeres / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; C107348:unc-45 protein, C elegans