John Cannon, PhD

Protein phosphorylation is a well-studied post-translational modification that regulates many aspects of protein function. Dr. Cannon uses a combination of powerful yeast molecular genetic techniques and computer simulations to decipher protein phosphorylation regulation from the pathway to atomic level descriptions. Dr. Cannon uses classical yeast genetics to identify protein phosphatase-1 (PP1) and a critical PP1 regulator, I2, based on their control of glycogen metabolism. Further biochemical analysis showed that I2 modulates PP1 function in yeast like all eukaryotic cells by its phosphorylation. I2 phosphorylation activates the PP1-I2 protein phosphatase activity without dissociation. Computer simulations of PP1-I2 molecular dynamics provide atomic level data about how phosphorylation in the unstructured I2 communicates with the I2 region near PP1 active site. This analysis has uncovered a novel method of phosphorylation control that does not exploit the phosphate charge.