Special Seminar - Wed., January 8
|Event Date:||January 8, 2014|
The seminar is entitled "“Molecular Mechanisms of Phospholipase Cβ Regulation.” Phospholipase Cβ (PLCβ) enzymes are key regulators of intracellular calcium levels and are essential for normal cardiovascular function. Dysregulation of PLCβ activity results in profound cellular changes, including cardiac hypertrophy and heart failure. PLCβ enzymes are characterized by very low basal activity and can be potently activated by extracellular signals via direct interactions with the heterotrimeric G proteins Gαq and Gβγ. However, the molecular basis of PLCβ autoinhibition and its activation by Gαq have remained poorly defined. A better understanding of these mechanisms is essential for the development novel therapeutic approaches to treat cardiovascular disease. Recent crystal structures have captured images of PLCβ in its autoinhibited basal state and in complex with Gαq. These structures, along with associated functional studies, define specific regions within the unique PLCβ C-terminal extension that contribute to regulation, Gαq binding, and membrane association. Taken together, these studies reveal an unanticipated allosteric mechanism of PLCβ activation and describe a sophisticated role for the C-terminal coiled-coil domain in dictating both membrane binding and the overall orientation of the signaling complex.
Dr. Lyon is a candidate for an Assistant Professor position in the Department of Chemistry.