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Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-subunit Gpa1p identify a receptor subtype-biased mating defect. 1998

S M DeSimone, and J Kurjan
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington 05405-0068, USA.

The response to pheromone in Saccharomyces cerevisiae involves a heterotrimeric G protein composed of Gpa1p (alpha subunit), Ste4p (beta) and Ste18p (gamma). The switch II region of G alpha subunits is involved in several protein-protein interactions and an intrinsic GTPase activity. To investigate the role of this region of Gpa1p, we have analyzed the effect of switch II mutations. The Q323 analog in G alpha subunits and Ras is implicated in GTP hydrolysis. Mutation of the Q323 residue of Gpa1p resulted in constitutive activation of the pheromone response pathway and eliminated the ability to interact with Ste4p, consistent with a defect in GTPase activity. Mutation of residue A59 of Ras and the analogous G alphas residue has had quite different effects. The analogous Gpa1p G321T mutation resulted in phenotypes consistent with a less severe GTPase defect, but also led to an unexpected mating phenotype: mating was decreased in both mating types, but the defect was 1000-fold more severe in alpha cells than in a cells. In addition the G321T mutation resulted in an unusual pheromone response phenotype. We discuss the possibility that these phenotypes may reflect a differential role for the switch II region in activation by the a- and alpha-factor receptors.

UI MeSH Term Description Entries
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011487 Protein Conformation The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). Conformation, Protein,Conformations, Protein,Protein Conformations
D005656 Fungal Proteins Proteins found in any species of fungus. Fungal Gene Products,Fungal Gene Proteins,Fungal Peptides,Gene Products, Fungal,Yeast Proteins,Gene Proteins, Fungal,Peptides, Fungal,Proteins, Fungal
D005800 Genes, Fungal The functional hereditary units of FUNGI. Fungal Genes,Fungal Gene,Gene, Fungal
D005812 Genes, Switch Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation. Switch Genes,Switching Complex,Switch Complexes,Switching Complexes,Complex, Switching,Complexes, Switch,Complexes, Switching,Gene, Switch,Switch Gene
D012441 Saccharomyces cerevisiae A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement. Baker's Yeast,Brewer's Yeast,Candida robusta,S. cerevisiae,Saccharomyces capensis,Saccharomyces italicus,Saccharomyces oviformis,Saccharomyces uvarum var. melibiosus,Yeast, Baker's,Yeast, Brewer's,Baker Yeast,S cerevisiae,Baker's Yeasts,Yeast, Baker
D012724 Sex Attractants Pheromones that elicit sexual attraction or mating behavior usually in members of the opposite sex in the same species. Copulins,Pheromones, Sexual,Sex Pheromones,Sexual Pheromone,Sex Attractant,Sex Pheromone,Attractant, Sex,Attractants, Sex,Pheromone, Sex,Pheromone, Sexual,Pheromones, Sex,Sexual Pheromones
D017354 Point Mutation A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. Mutation, Point,Mutations, Point,Point Mutations
D043802 GTP-Binding Protein alpha Subunits, Gq-G11 A family of heterotrimeric GTP-binding protein alpha subunits that activate TYPE C PHOSPHOLIPASES dependent signaling pathways. The Gq-G11 part of the name is also spelled Gq/G11. G alpha q Protein,G-Protein, Gq,G-Protein, Gq alpha Family,G-Protein, Gq-G11 alpha Family,G alpha Protein q,G alpha11 Protein,G-Protein, G11,G-Protein, Gq-G11,GTP-Binding Protein alpha Subunit, G11,GTP-Binding Protein alpha Subunit, Gq,Galpha11 Protein,Galphaq Protein,Gq Protein,Gq-G11 G-Protein Family,Gq-G11 G-Proteins,Family, Gq-G11 G-Protein,G Protein, G11,G Protein, Gq,G Protein, Gq G11,G Protein, Gq G11 alpha Family,G Protein, Gq alpha Family,G-Protein Family, Gq-G11,G-Proteins, Gq-G11,G11 G-Protein,GTP Binding Protein alpha Subunit, G11,GTP Binding Protein alpha Subunit, Gq,GTP Binding Protein alpha Subunits, Gq G11,Gq G-Protein,Gq G11 G Protein Family,Gq G11 G Proteins,Gq-G11 G-Protein,Protein, G alpha11,Protein, Galpha11,alpha11 Protein, G
D044385 GTP-Binding Protein alpha Subunits The GTPase-containing subunits of heterotrimeric GTP-binding proteins. When dissociated from the heterotrimeric complex these subunits interact with a variety of second messenger systems. Hydrolysis of GTP by the inherent GTPase activity of the subunit causes it to revert to its inactive (heterotrimeric) form. The GTP-Binding protein alpha subunits are grouped into families according to the type of action they have on second messenger systems. G-Protein alpha Subunit,GTP-Binding Protein alpha Subunit,G Protein alpha Subunit,GTP Binding Protein alpha Subunit,GTP Binding Protein alpha Subunits,alpha Subunit, G-Protein

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