The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. Elegans

Cell. 2013 Jan 17;152(1-2):183-95. doi: 10.1016/j.cell.2012.12.025.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP90 Heat-Shock Proteins / metabolism
  • Models, Molecular
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Myofibrils / metabolism*
  • Promoter Regions, Genetic
  • Protein Folding
  • Protein Structure, Tertiary
  • Sarcomeres / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • unc-45 protein, C elegans

Associated data

  • PDB/4I2W
  • PDB/4I2Z