Dr. Trevor Creamer of the University of Kentucky's Molecular and Cellular Biochemistry Department will be presenting a seminar entitled, The Disordered Regulation of Calcineurin.

Abstract: Calcineurin (CaN) is a highly regulated Ser/Thr protein phosphatase that plays critical roles in learning and memory, cardiac development and function, and immune system activation. Alterations in CaN regulation contribute to multiple disease states such as Down syndrome, cardiac hypertrophy, Alzheimer’s disease, and autoimmune disease. Despite its importance, CaN regulation is not well understood at the molecular level. Full CaN activation requires binding of calcium-loaded calmodulin (CaM), however little is known about how CaM binding leads to CaN activation. I will present evidence that the 95 residue CaN regulatory domain, where the CaM binding region is located, is disordered. The binding of CaM to CaN results in the regulatory domain folding. Folding of this regulatory domain in turn causes an autoinhibitory domain to be ejected from CaN’s active site. It is this binding-induced disorder-to-order transition that is responsible for the activation of CaN by CaM.

Facutly Host: Dr. Jason DeRouchey