Description:

The Department of Pharmacology and the Driskill Graduate Program welcome Brian Kobilka, MD, as our lecturer for the 5th Annual Narahashi Lecture and Distinguished Lectures in Life Sciences.

Please join us for a reception immediately following the lecture in Ryan Family Atrium.

Brian K. Kobilka, M.D.
2012 Nobel Prize in Chemistry
Professor, Department of Molecular & Cellular Physiology
Helene Irwin Fagan Chair in Cardiology
Stanford School of Medicine

"Structural Insights into the Dynamic Process of G Protein Coupled Receptor Activation"

G protein coupled receptors (GPCRs) conduct the majority of transmembrane responses to hormones and neurotransmitters, and mediate the senses of sight, smell and taste. The 2 adrenergic receptor (2AR), the M2 muscarinic receptor and the mu-opioid receptor are prototypical Family A GPCRs. We have obtained three-dimensional structures of these receptors in inactive and active conformations, as well as a structure of the 2AR in complex with the G protein Gs. Comparison of these structures provides insights into common mechanisms for propagation of conformational changes from the agonist binding pocket to the G protein coupling interface. Crystal structures of inactive and active states may give the impression that GPCRs behave as simple two-state systems. However, cellular signaling assays reveal that many GPCRs signal through more than one G protein isoform, and through G protein independent pathways. This complex functional behavior provides evidence for the existence of multiple functionally distinct conformational states. We have used fluorescence, EPR and NMR spectroscopy to study the dynamic properties of several GPCRs. I will discuss what we these studies have taught us about allosteric regulation of GPCR structure by G proteins and ligands.