ArticleThe Journal of biological chemistry2008
Unc45 activates Hsp90-dependent folding of the myosin motor domain.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 94 citations in OpenAlex.
- Dynamic Proximity Networks of Myosin-19 (Myo19) and its Mitochondrial Receptors Miro2 and Metaxin-3.Molecular & cellular proteomics : MCP · 2026Article
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- MYH9 mutations differentially stabilize non-muscle myosin II filaments and induce distinct cellular aggregation phenotypes.Cellular and molecular life sciences : CMLS · 2026Article
- S2Tag, a novel affinity tag for the capture and immobilization of coiled-coil proteins: Application to the study of human β-cardiac myosin.The Journal of biological chemistry · 2025Article
- Altered chaperone-nonmuscle myosin II interactions drive pathogenicity of the UNC45A c.710T>C variant in osteo-oto-hepato-enteric syndrome.JCI insight · 2025Article
- Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 2024Review
- Review
- Article
- UCS Chaperone Folding of the Myosin Head: A Function That Evolved before Animals and Fungi Diverged from a Common Ancestor More than a Billion Years Ago.Biomolecules · 2022Review
- A myosin chaperone, UNC-45A, is a novel regulator of intestinal epithelial barrier integrity and repair.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- RNA-Seq analysis of a Pax3-expressing myoblast clone in-vitro and effect of culture surface stiffness on differentiation.Scientific reports · 2022Article
- Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies.Frontiers in physiology · 2022Review
- Molecular chaperone Hsp90 protects KCBP from degradation by proteasome in Dunaliella salina cells.Folia microbiologica · 2021Article
- Proteins in plasma as a potential biomarkers diagnostic for pelvic organ prolapse.Annals of translational medicine · 2021Article
- hsp-90 and unc-45 depletion induce characteristic transcriptional signatures in coexpression cliques of C. elegans.Scientific reports · 2021Article
- Spectrum ofGenes · 2021Article
- General Structural and Functional Features of Molecular Chaperones.Advances in experimental medicine and biology · 2021Article
- Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.Nature communications · 2019Article
- Myoglobin maturation is driven by the hsp90 chaperone machinery and by soluble guanylyl cyclase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Myosin folding and assembly in striated muscle are mediated by the general chaperones Hsc70 and Hsp90 and involve a myosin-specific co-chaperone related to the Caenorhabditis elegans gene unc-45. Two unc-45 genes are found in vertebrates, a general cell isoform, unc45a, and a striated muscle-specific isoform, unc45b. We have investigated the role of both isoforms of mouse Unc45 in myosin folding using an in vitro synthesis and folding assay. A smooth muscle myosin motor domain (MD) fused to green fluorescent protein (GFP) (MD::GFP) was used as substrate, and folding was measured by native gel electrophoresis and functional assays. In the absence of Unc45, the MD::GFP chimera folds poorly. Addition of either Unc45a or Unc45b dramatically enhances the folding in a reaction that is dependent on Hsp90 ATPase activity. Unc45a is more effective than Unc45b with a higher apparent affinity and greater extent of folding. The Unc45-Hsp90 chaperone complex acts late in the folding pathway and promotes motor domain maturation after release from the ribosome. Unc45a behaves kinetically as an activator of the folding reaction by stimulating the rate of the Hsp90-dependent folding by >20-fold with an apparent K(act) of 33 nm. This analysis of vertebrate Unc45 isoforms clearly demonstrates a direct role for Unc45 in Hsp90-mediated myosin motor domain folding and highlights major differences between the isoforms in substrate specificity and mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.