Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity.
Mutations in conserved residues of the myosin chaperone UNC-45 result in both reduced stability and chaperoning activity.
复制标题
肌球蛋白伴侣 UNC-45 保守残基的突变会导致稳定性和伴侣活性降低。
DOI：
10.1002/pro.4180
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Oberhauser,AndresF
中科院分区：
文献类型：
--
作者：
Moncrief,Taylor;Matheny,CourtneyJ;Gaziova,Ivana;Miller,JohnM;Qadota,Hiroshi;Benian,GuyM;Oberhauser,AndresF
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 vivoC. elegansexperiments 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.
