The UNC-45 myosin chaperone: from worms to flies to vertebrates

Int Rev Cell Mol Biol. 2014:313:103-44. doi: 10.1016/B978-0-12-800177-6.00004-9.

Abstract

UNC-45 (uncoordinated mutant number 45) is a UCS (UNC-45, CRO1, She4p) domain protein that is critical for myosin stability and function. It likely aides in folding myosin during cellular differentiation and maintenance, and protects myosin from denaturation during stress. Invertebrates have a single unc-45 gene that is expressed in both muscle and nonmuscle tissues. Vertebrates possess one gene expressed in striated muscle (unc-45b) and another that is more generally expressed (unc-45a). Structurally, UNC-45 is composed of a series of α-helices connected by loops. It has an N-terminal tetratricopeptide repeat domain that binds to Hsp90 and a central domain composed of armadillo repeats. Its C-terminal UCS domain, which is also comprised of helical armadillo repeats, interacts with myosin. In this chapter, we present biochemical, structural, and genetic analyses of UNC-45 in Caenorhabditis elegans, Drosophila melanogaster, and various vertebrates. Further, we provide insights into UNC-45 functions, its potential mechanism of action, and its roles in human disease.

Keywords: Chaperone; Hsp90; Muscle; Myosin; TPR domain; UCS protein; UNC-45.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Chaperones / chemistry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Molecular Sequence Data
  • Muscle Proteins
  • Mutation
  • Myosins / metabolism*
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Structure-Activity Relationship
  • Xenopus / genetics
  • Xenopus / metabolism
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • Zebrafish / genetics
  • Zebrafish / metabolism
  • Zebrafish Proteins / chemistry
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • Muscle Proteins
  • UNC-45 protein, Drosophila
  • Unc45 protein, mouse
  • Unc45b protein, zebrafish
  • Xenopus Proteins
  • Zebrafish Proteins
  • unc-45 protein, C elegans
  • Myosins