Interdisciplinary Initiatives Program Round 1 - 2000

Brian Kobilka, Molec. & Cell. Phys.
Gadi Peleg, Chemistry
Richard Zare, Chemistry
Peiman Ghanouni, Molec. & Cell. Phys

G protein coupled receptors (GPCR) constitute one of the largest families of integral membrane proteins and are responsible for the majority of transmembrane signal transduction. They represent the largest group of targets for drug development.

The b2 adrenergic receptor (b2AR) is a prototypical member of this large family of integral membrane proteins. It serves as a paradigm for GPCR activation and regulation. We used single-molecule spectroscopy to study drug-induced conformational changes in the b2AR in an effort to understand the mechanism by which agonist binding to the extracellular surface of the receptor leads to intracellular G protein activation.

These studies provide insight into the conformational heterogeneity of G protein coupled receptors in the presence and absence of a bound agonist.