ArticleProceedings of the National Academy of Sciences of the United States of America1996
Mutation of Pro-258 in transmembrane domain 6 constitutively activates the G protein-coupled alpha-factor receptor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38 citing papers in PubMed, 98 citations in OpenAlex.
- Comparison of Experimental Approaches Used to Determine the Structure and Function of the Class D G Protein-Coupled Yeast α-Factor Receptor.Biomolecules · 2022Review
- A Paradigm for Peptide Hormone-GPCR Analyses.Molecules (Basel, Switzerland) · 2020Review
- Yeast GPCR signaling reflects the fraction of occupied receptors, not the number.Molecular systems biology · 2016Article
- Variable Dependence of Signaling Output on Agonist Occupancy of Ste2p, a G Protein-coupled Receptor in Yeast.The Journal of biological chemistry · 2016Article
- Analysis of random PCR-originated mutants of the yeast Ste2 and Ste3 receptors.MicrobiologyOpen · 2016Article
- Quantification of mutation-derived bias for alternate mating functionalities of the Saccharomyces cerevisiae Ste2p pheromone receptor.Journal of biochemistry · 2016Article
- Identification of destabilizing and stabilizing mutations of Ste2p, a G protein-coupled receptor in Saccharomyces cerevisiae.Biochemistry · 2015Article
- Functional and physical interactions among Saccharomyces cerevisiae α-factor receptors.Eukaryotic cell · 2012Article
- Identifying functionally important conformational changes in proteins: activation of the yeast α-factor receptor Ste2p.Journal of molecular biology · 2012Article
- The seven-transmembrane receptor Gpr1 governs processes relevant for the antagonistic interaction of Trichoderma atroviride with its host.Microbiology (Reading, England) · 2012Article
- Differential interactions of fluorescent agonists and antagonists with the yeast G protein coupled receptor Ste2p.Journal of molecular biology · 2011Article
- Identification of residue-to-residue contact between a peptide ligand and its G protein-coupled receptor using periodate-mediated dihydroxyphenylalanine cross-linking and mass spectrometry.The Journal of biological chemistry · 2010Article
- International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors.Pharmacological reviews · 2010Article
- Signaling-sensitive amino acids surround the allosteric ligand binding site of the thyrotropin receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2010Article
- Assessment of constitutive activity of a G protein-coupled receptor, CPR2, in Cryptococcus neoformans by heterologous and homologous methods.Methods in enzymology · 2010Article
- Strategies for isolating constitutively active and dominant-negative pheromone receptor mutants in yeast.Methods in enzymology · 2010Article
- Synthetic morphology using alternative inputs.PloS one · 2009Article
- A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans.The EMBO journal · 2009Article
- Magnificent seven: roles of G protein-coupled receptors in extracellular sensing in fungi.FEMS microbiology reviews · 2008Review
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The alpha-factor pheromone receptor stimulates MATa yeast cells to undergo conjugation. The receptor contains seven transmembrane domains that function in ligand binding and in transducing a signal to the cytoplasmic receptor sequences to mediate G protein activation. A genetic screen was used to isolate receptor mutations that constitutively signal in the absence of alpha-factor. The Pro-258-->Leu (P258L) mutation caused constitutive receptor signaling that was equivalent to about 45% of the maximum level observed in wild-type cells stimulated with alpha-factor. Mutations of both Pro-258 and the adjacent Ser-259 to Leu increased constitutive signaling to > or = 90% of the maximum level. Since Pro-258 occurs in the central portion of transmembrane domain 6, and since proline residues are expected to cause a kink in alpha-helical domains, the P258L mutation is predicted to alter the structure of transmembrane domain 6. The P258L mutation did not result in a global distortion of receptor structure because alpha-factor bound to the mutant receptors with high affinity and induced even higher levels of signaling. These results suggest that sequences surrounding Pro-258 may be involved in ligand activation of the receptor. Conformational changes in transmembrane domain 6 may effect a change in the adjacent sequences in the third intracellular loop that are thought to function in G protein activation. Greater than 90% of all G protein-coupled receptors contain a proline residue at a similar position in transmembrane domain 6, suggesting that this aspect of receptor activation may be conserved in other receptors.
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