Mutations in conserved residues of the myosin chaperone UNC ‐45 result in both reduced stability and chaperoning activity
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 protein stability. This suggests that these mutations only cause protein instability in the in vivo setting and that these conserved regions may be involved in UNC‐45 protein stability/regulation via posttranslational modifications, protein–protein interactions, or some other unknown mechanism.
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Kathrin Gieseler
Owen Thompson, Mark Edgley, Pnina Strasbourger et al.
Eric F. Pettersen, Thomas D. Goddard, Conrad C. Huang et al.
Lawrence A Kelley, Michael J.E Sternberg
T. Schwede
Marcelo M. Santoro, D. W. Bolen
Kathy Huynh, Carrie L. Partch
R. Chenna
F. Corpet
- Published
- Sep 28, 2021
- Vol/Issue
- 30(11)
- Pages
- 2221-2232
- License
- View
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