Presents the Friday Keck Center Teleconference*
NMR Analysis of GPCR Activation and G protein Interactions
Kevin Ridge, Ph.D.,
Associate Professor of Biochemistry and Molecular Biology University of Texas Health Science Center at Houston Medical School
4:00 pm Friday
Dec. 7th , 2007
(Refreshments at 3:45)
5.521 Levin Hall
Abstract: G protein-coupled receptors (GPCRs) represent a diverse group of seven transmembrane helix receptors that require ligand-dependent activation to initiate heterotrimeric (alpha-beta-gamma) G-protein mediated intracellular signaling cascades. Activation of a G protein by its agonist-stimulated GPCR (R*) requires the propagation of structural signals from the G protein interacting surface on R* to the binding surface of the G protein gamma-subunit, and ultimately to the guanine nucleotide-binding pocket to trigger GDP/GTP exchange. The structural basis for the interaction of R* with its cognate G protein, and the subsequent activation of the G protein by R*,is not well understood. Using rhodopsin as a model GPCR, conformational changes upon formation of R* have been monitored by high-resolution NMR spectroscopy using selective isotope labeling of lysine residues predominantly along the G protein interacting cytoplasmic surface. Conformational changes in uniformly isotope labeled G-alpha have also been probed by NMR after heterotrimer formation with unlabeled G protein beta-gamma-subunits and during the course of R*-stimulated guanine nucleotide exchange. Our results to date suggest that high-resolution NMR can be effectively utilized to probe the structural basis of GPCR and G protein activation. ( http://www.uth.tmc.edu/bmb/faculty/Ridge/Ridge.html )
