Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity.

ABSTRACT: Proper muscle development and function depend on myosin being properly folded and integrated into the thick filament structure. For this to occur the myosin chaperone UNC-45, or UNC-45B, must be present and able to chaperone myosin. Here we use a combination of in vivo C. elegans experiments and in vitro biophysical experiments to analyze the effects of six missense mutations in conserved regions of UNC-45/UNC-45B. We found that the phenotype of paralysis and disorganized thick filaments in 5/6 of the mutant nematode strains can likely be attributed to both reduced steady state UNC-45 protein levels and reduced chaperone activity. Interestingly, the biophysical assays performed on purified proteins show that all of the mutations result in reduced myosin chaperone activity but not overall p

SUBMITTER: Moncrief T 

PROVIDER: S-EPMC8521276 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature