UNC-45 assisted myosin folding depends on a conserved FX₃HY motif implicated in Freeman Sheldon Syndrome.

ABSTRACT: Myosin motors are critical for diverse motility functions, ranging from cytokinesis and endocytosis to muscle contraction. The UNC-45 chaperone controls myosin function mediating the folding, assembly, and degradation of the muscle protein. Here, we analyze the molecular mechanism of UNC-45 as a hub in myosin quality control. We show that UNC-45 forms discrete complexes with folded and unfolded myosin, forwarding them to downstream chaperones and E3 ligases. Structural analysis of a minimal chaperone:substrate complex reveals that UNC-45 binds to a conserved FX₃HY motif in the myosin motor domain. Disrupting the observed interface by mutagenesis prevents myosin maturation leading to protein aggregation in vivo. We also show that a mutation in the FX₃HY motif linked to

SUBMITTER: Vogel A 

PROVIDER: S-EPMC11272940 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature