Dr. Kevin Ridge, Associate Professor

Structural aspects of g-protein coupled receptor function

The research in my laboratory is primarily focused on the dynamic aspects of integral membrane protein structure. Particular emphasis is given to members of the superfamily of G-protein coupled receptors (GPCR's) sharing the seven-transmembrane-helix structural motif. Biochemical, biophysical, and structural approaches are being used to study the molecular mechanisms underlying GPCR function using the HIV-1 coreceptor CCR5 and the visual photoreceptor rhodopsin as models. Specifically, high-resolution structural methods are being used to elucidate the molecular details of ligand and viral recognition (CCR5) and G-protein mediated signal transduction (rhodopsin, see Figure). It is anticipated that these efforts will have a fundamental impact on our structural understanding of the mechanisms governing signal transfer in these GPCR's while at the same time advancing a general strategy for studying GPCR's involved in other signaling pathways.

A second research area is focused on the development and application of general approaches for the large-scale expression and purification of GPCR's. The main emphasis in these studies is to devise methods that facilitate the optimal expression of properly folded protein in eukaryotic hosts and the one-step generation and purification of native-like, functionally intact receptors for structural studies.

Crystal structures for rhodopsin and the heterotrimeric G-protein transducin highlighting the signal transfer process leading to guanine nucleotide exchange

Abdulaev NG, Mao X, Ramon E, Ngo T, Mysliwy J, Marino JP, Ridge KD. Designing point mutants to detect structural coupling in a heterotrimeric G protein alpha-subunit by NMR spectroscopy. Photochem Photobiol. 85:431-436, 2009.

Ramon E, Mao X, Ridge KD. Studies on the stability of the human cone visual pigments. Photochem Photobiol. 85:509-516, 2009.

Ridge, K. D. and Palczewski, K. (2007) Visual rhodopsin sees the light: Structure and mechanism of G protein signaling, J. Biol. Chem. 282, 9297-9301.

Abdulaev, N. G., Ngo, T., Ramon, E., Brabazon, D. M. Marino, J. P. and  Ridge, K. D. (2006) The Receptor-bound "Empty Pocket" State of the Heterotrimeric G-protein α-Subunit is Conformationally Dynamic.  Biochemistry 45, 12986-12997.

Ridge, K. D., Marino, J. P., Ngo, T., Ramon, E., Brabazon, D. M. and Abdulaev, N. G. (2006) NMR Analysis of Rhodopsin-Transducin Interactions. Vision Res. 46,  4482-4492.

Ridge, K. D., Abdulaev, N. G., Zhang, C., Ngo, T., Brabazon, D. M. and Marino, J. P. (2006) Conformational Changes Associated with Receptor Stimulated Guanine Nucleotide Exchange in a Heterotrimeric G-protein α-Subunit: NMR Analysis of GTPγS-bound States. J. Biol. Chem. 281, 7635-7648.

Silin, V. I., Karlik, E. A., Ridge, K. D. and Vanderah, D. J. (2006) Development of Surface-based Assays for Transmembrane Proteins: Selective Immobilization of Functional CCR5, a G protein-coupled Receptor. Anal. Biochem. 349, 247-253.

Abdulaev, N. G., Ngo, T., Zhang, C., Dinh, A., Brabazon, D. M., Ridge, K. D. and Marino, J. P. (2005) Heterotrimeric G-protein α-Subunit Adopts a “Preactivated” Conformation When Associated with βγ-Subunits. J. Biol. Chem. 280, 38071-38080.

Abdulaev, N. G., Zhang, C., Dinh, A., Ngo, T., Bryan, P. N., Brabazon, D. M., Marino, J. P. and Ridge, K. D. (2005) Bacterial Expression and One-step Purification of an Isotope-labeled Heterotrimeric G-protein α-subunit. J. Biomol. NMR 32, 31-40.

Abdulaev, N. G. and Ridge, K. D. (2005) Structural and Functional Aspects of the Mammalian Rod Cell Photoreceptor Rhodopsin, in Handbook of Photosensory Receptors (Briggs, W. R. and Spudich, J. L., eds.), pp. 77-92, Wiley-VCH Verlag GmbH Co. KGaA, Weinheim, Germany.

Ridge, K. D., Abdulaev, N. G., Sousa, M. and Palczewski, K. (2003) Phototransduction: Crystal Clear, Trends Biochem. Sci. 28, 479-487.

Brabazon, D. M., Abdulaev, N. G., Marino, J. P. and Ridge, K. D. (2003) Evidence for Structural Changes in Carboxyl-terminal Peptides of Transducin α-subunit upon Binding a Soluble Mimic of Light-activated Rhodopsin, Biochemistry 42, 302-311.

Abdulaev, N. G., Strassmaier, T. T., Ngo, T., Chen, R., Luecke, H., Oprian, D. D. and Ridge, K. D. (2002) Grafting Segments from the Extracellular Surface of CCR5 onto a Bacteriorhodopsin Transmembrane Scaffold Confers HIV-1 Coreceptor Activity. Structure 10, 515-525.

Search PubMed for a complete list of Dr. Ridge's publications.