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Publication Abstract from PubMed

Myosin is a motor protein that is essential for a variety of processes ranging from intracellular transport to muscle contraction. Folding and assembly of myosin relies on a specific chaperone, UNC-45. To address its substrate-targeting mechanism, we reconstitute the interplay between Caenorhabditis elegans UNC-45 and muscle myosin MHC-B in insect cells. In addition to providing a cellular chaperone assay, the established system enabled us to produce large amounts of functional muscle myosin, as evidenced by a biochemical and structural characterization, and to directly monitor substrate binding to UNC-45. Data from in vitro and cellular chaperone assays, together with crystal structures of binding-deficient UNC-45 mutants, highlight the importance of utilizing a flexible myosin-binding domain. This so-called UCS domain can adopt discrete conformations to efficiently bind and fold substrate. Moreover, our data uncover the molecular basis of temperature-sensitive UNC-45 mutations underlying one of the most prominent motility defects in C. elegans.

Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.,Hellerschmied D, Lehner A, Franicevic N, Arnese R, Johnson C, Vogel A, Meinhart A, Kurzbauer R, Deszcz L, Gazda L, Geeves M, Clausen T Nat Commun. 2019 Oct 21;10(1):4781. doi: 10.1038/s41467-019-12667-8. PMID:31636255^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.