6QDJ

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

Summary for 6QDJ

• Entry DOI: 10.2210/pdb6qdj/pdb
• Descriptor: Myosin-4, ADENOSINE-5'-DIPHOSPHATE, GLYCEROL, ... (8 entities in total)
• Functional Keywords: myosin, mhc-b, unc-54, motor protein
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 1
• Total formula weight: 92377.28

Authors

Meinhart, A.,Clausen, T.,Arnese, R. (deposition date: 2019-01-02, release date: 2019-10-30, Last modification date: 2024-01-24)

Primary citation

Hellerschmied, D.,Lehner, A.,Franicevic, N.,Arnese, R.,Johnson, C.,Vogel, A.,Meinhart, A.,Kurzbauer, R.,Deszcz, L.,Gazda, L.,Geeves, M.,Clausen, T.
Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.
Nat Commun, 10:4781-4781, 2019

PubMed 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.

PubMed: 31636255
DOI: 10.1038/s41467-019-12667-8

Experimental method

X-RAY DIFFRACTION (1.884 Å)