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Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.


ABSTRACT: 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.

SUBMITTER: Hellerschmied D 

PROVIDER: S-EPMC6803673 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.

Hellerschmied Doris D   Lehner Anita A   Franicevic Nina N   Arnese Renato R   Johnson Chloe C   Vogel Antonia A   Meinhart Anton A   Kurzbauer Robert R   Deszcz Luiza L   Gazda Linn L   Geeves Michael M   Clausen Tim T  

Nature communications 20191021 1


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  ...[more]

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