Yeast assays for G-protein-coupled receptors.
Yeast assays for G-protein-coupled receptors have many attractions due to their simplicity, low cost, and lack of endogenous receptors. Since the first report of functional coupling of the human beta 2 adrenergic receptor to the yeast pheromone-response pathway in 1990, the technology has developed to a point at which more than 30 heterologous GPCRs are now published to couple. Major breakthroughs have come from an understanding of receptor-G protein interactions, alongside advances in knowledge of the structure of heterotrimeric G proteins. Yeast screens have been used to identify ligands both from compound collections and through the autocrine expression of peptide libraries. Yeast genetics has also been applied to a functional analysis of GPCRs and peptide ligands. In this review we describe the historical development of yeast GPCR assay systems and their current applications.
Dowell
S J
SJ
GlaxoSmithkline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK. sd14041@gsk.com
Brown
A J
AJ
D001671:Biochemistry / Q000379:methods*; D001709:Biotechnology / Q000379:methods; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry; D006801:Humans; D008024:Ligands; D008550:Melatonin / Q000494:pharmacology; D008954:Models, Biological; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry; D010675:Pheromones / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry; D044094:Receptors, Melatonin; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry
D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D008024:Ligands; D010455:Peptides; D010675:Pheromones; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; C084294:STE18 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C067576:Ste4 protein, S cerevisiae; D019204:GTP-Binding Proteins; C084293:GPA1 protein, S cerevisiae; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins; D008550:Melatonin