Science Seminar

Striated muscle UNC-45 (SM UNC-45 or UNC-45B) is a chaperone specific for cardiac and skeletal muscle myosins, regulating their folding, assembly into thick filaments, interaction with other sarcomeric proteins, and degradation. GATA-4 is a transcription factor that regulates the expression of several cardiac muscle genes, including myosin’s. Chen et. al., (2012) first reported potential physical interaction between UNC-45B and GATA-4 that enhanced the activity of the transcription factor. In the present study, we have identified the UCS domain of UNC-45B as the preferred binding region for its interaction with GATA-4. In addition, studies using mutant proteins have identified certain structural modules and residues in UNC-45B important for interaction with GATA-4. Ongoing experiments include spectroscopic, pull-down and chaperoning assays, and computational docking studies to characterize the nature of this novel chaperone-transcription factor interaction, identify critical amino acid residues, and obtain binding affinities. By modulating GATA-4 transcriptional activity, UNC-45B shows potential to exert both short-term (protein level) and long-term (gene level) controls over myosin and therefore muscle structure and function.