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

@article{Gazda2013TheMC,
  title={The Myosin Chaperone UNC-45 Is Organized in Tandem Modules to Support Myofilament Formation in C. elegans},
  author={Linn Gazda and Wojciech Pokrzywa and Doris Hellerschmied and Thomas L{\"o}we and Ignasi Forn{\'e} and Felix Mueller-Planitz and Thorsten Hoppe and Tim Clausen},
  journal={Cell},
  year={2013},
  volume={152},
  pages={183 - 195}
}
Summary 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… Expand
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TLDR
In this chapter, biochemical, structural, and genetic analyses of UNC-45 are presented in Caenorhabditis elegans, Drosophila melanogaster, and various vertebrates to provide insights into UNC- 45 functions, its potential mechanism of action, and its roles in human disease. Expand
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TLDR
Structural analyses suggest that UNC-45 proteins form elongated oligomers that serve as scaffolds to recruit Hsp90 and/or Hsp70 to form a multi-protein chaperoning complex that assists myosin heads to fold and simultaneously organize them into myofibrils. Expand
UNC-45B chaperone: the role of its domains in the interaction with the myosin motor domain.
TLDR
It is concluded that while both the UCS and the Central domains bind the myosin head with high affinity, only the UCS domain displays chaperone activity. Expand
Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity
TLDR
The biophysical assays performed on purified proteins show that all of the mutations result in reduced myosin chaperone activity but not overall protein stability, suggesting that these mutations only cause protein instability in the in vivo setting and that these conserved regions may be involved in UNC-45 protein stability/ regulation via post translational modifications, protein-protein interactions, or some other unknown mechanism. Expand
Identification of New Protein Interactions of UNC-45, a Myosin Molecular Chaperone, in Drosophila melanogaster
TLDR
A deficiency region (7783) where the cross yielded lethality for double heterozygotes is identified and putatively mapped to the SLY1homologous (CG3539) gene, which points to SLY-1 homologous as an important gene involved in muscle function and development. Expand
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