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
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Crystallography, X-Ray
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Mice
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Models, Molecular
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Molecular Chaperones / chemistry
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism*
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Molecular Sequence Data
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Muscle Proteins
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Mutation
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Myosins / metabolism*
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Protein Conformation
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Protein Interaction Domains and Motifs
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Structure-Activity Relationship
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Xenopus / genetics
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Xenopus / metabolism
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Xenopus Proteins / genetics
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Xenopus Proteins / metabolism
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Zebrafish / genetics
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Zebrafish / metabolism
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Zebrafish Proteins / chemistry
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism
Substances
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Caenorhabditis elegans Proteins
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Molecular Chaperones
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Muscle Proteins
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UNC-45 protein, Drosophila
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Unc45 protein, mouse
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Unc45b protein, zebrafish
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Xenopus Proteins
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Zebrafish Proteins
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unc-45 protein, C elegans
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Myosins