Date of Award
Doctor of Philosophy
Jeffrey M. Becker
David Brian, Elizabeth E. Howell, John W. Koontz
G protein-coupled receptors (GPCRs) are a class of integral membrane receptor proteins that are characterized by seven-transmembrane (7TM) domains connected by intracellular and extracellular loops, an extracellular N-terminus, and an intracellular C-terminus. To date more than 1000 GPCRs have been identified, and these proteins recognize neurotransmitters, sensory molecules and chemotactic agents. These receptors are involved in the control of many aspects of metabolism and play important roles in diverse processes such as pain perception, growth and blood pressure regulation, and viral pathogenesis. Therefore, these proteins became important target for therapeutic agents and recent reports indicate that nearly 40% of drugs currently prescribed for human ailments target this family of proteins.
The tridecapeptide α-factor pheromone(W1H2W3L4Q5L6K7P8G9Q10P11M12Y13) of Saccharomyces cerevisiae and Ste2p, its cognate GPCR, have been used extensively as a model for peptide ligand-GPCR structure and function. The power of yeast genetic was used to examine the structure –function relationship of α-factor receptor. Upon the α-factor binding to Ste2p, a signal is transduced via an associated guanine-nucleotide binding protein initiating a cascade of events that leads to the mating of haploid yeast cells. As only two GPCRs and two G proteins are encoded in the S. cerevisiae genome, S. cerevisiae provides an ideal system to study the relation between a peptide ligand and its GPCR in the absence of interfering biological complexities.
Lee, Yong-Hun, "Studies on the Role of Specific Residues of the Saccharomyces α-factor Pheromone Receptor (Ste2p) in the Inactive and Active State. " PhD diss., University of Tennessee, 2005.