Key result
The myosin-directed chaperone UNC-45 forms linear protein chains that serve as a multisite docking platform for myosin molecules, coordinating their folding and assembly during muscle formation and aging.
The UNC-45 chaperone protein forms a chain that coordinates myosin folding and myofilament assembly, providing insights into muscle regeneration and myopathic diseases.
No immediate clinical implications; extends molecular framework for myosin assembly research in myopathies.
The activity and assembly of various myosin subtypes is coordinated by conserved UCS (UNC-45/CRO1/She4p) domain proteins. One founding member of the UCS family is the Caenorhabditis elegans UNC-45 protein important for the organization of striated muscle filaments. Our recent structural and biochemical results demonstrated that UNC-45 forms a protein chain with defined periodicity of myosin interaction domains. Intriguingly, the UNC-45 chain serves as docking platform for myosin molecules, which promotes ordered spacing and incorporation of myosin into contractile muscle sarcomeres. The physiological relevance of this observation was demonstrated in C. elegans by transgenic expression of UNC-45 chain formation mutants, which provokes defects in muscle structure and size. Collaborating with the molecular chaperones, Hsp70 and Hsp90, chain formation of UNC-45 links myosin folding with myofilament assembly. Here, we discuss our recent findings on the dynamic regulation of UNC-45 structure and stability in the context of muscle regeneration mechanisms that are affected in myopathic diseases and during aging.
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Pokrzywa et al. (2013) conducted a review in Muscle formation and aging. UNC-45 was evaluated. The myosin-directed chaperone UNC-45 forms linear protein chains that serve as a multisite docking platform for myosin molecules, coordinating their folding and assembly during muscle formation and aging.
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