The UNC-45 myosin chaperone: from worms to flies to vertebrates.
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.
Department of Biology, San Diego State University, San Diego, CA, USA.
Chi F
CF
Lee
Department of Biology, San Diego State University, San Diego, CA, USA.
Girish C
GC
Melkani
Department of Biology, San Diego State University, San Diego, CA, USA.
Sanford I
SI
Bernstein
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009154:Mutation; D009218:Myosins / Q000378:metabolism*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D013329:Structure-Activity Relationship; D014981:Xenopus / Q000235:genetics / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009124:Muscle Proteins; C550552:UNC-45 protein, Drosophila; C529478:Unc45 protein, mouse; C472790:Unc45b protein, zebrafish; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; C107348:unc-45 protein, C elegans; D009218:Myosins
Chaperone; Hsp90; Muscle; Myosin; TPR domain; UCS protein; UNC-45