ArticleScientific reports2017
The directed evolution of ligand specificity in a GPCR and the unequal contributions of efficacy and affinity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 22 citations in OpenAlex.
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- Pheromone Response and Mating Behavior in Fission Yeast.Microbiology and molecular biology reviews : MMBR · 2022Review
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- Role of Calcium Homeostasis in Modulating EMT in Cancer.Biomedicines · 2021Review
- Photostable and Proteolysis-Resistant Förster Resonance Energy Transfer-Based Calcium Biosensor.Analytical chemistry · 2020Article
- Selecting for Altered Substrate Specificity Reveals the Evolutionary Flexibility of ATP-Binding Cassette Transporters.Current biology : CB · 2020Article
- Engineering G protein-coupled receptor signalling in yeast for biotechnological and medical purposes.FEMS yeast research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
G protein-coupled receptors (GPCRs) must discriminate between hundreds of related signal molecules. In order to better understand how GPCR specificity can arise from a common promiscuous ancestor, we used laboratory evolution to invert the specificity of the Saccharomyces cerevisiae mating receptor Ste2. This GPCR normally responds weakly to the pheromone of the related species Kluyveromyces lactis, though we previously showed that mutation N216S is sufficient to make this receptor promiscuous. Here, we found that three additional substitutions, A265T, Y266F and P290Q, can act together to confer a novel specificity for K. lactis pheromone. Unlike wild-type Ste2, this new variant does not rely on differences in binding affinity to discriminate against its non-preferred ligand. Instead, the mutation P290Q is critical for suppressing the efficacy of the native pheromone. These two alternative methods of ligand discrimination were mapped to specific amino acid positions on the peptide pheromones. Our work demonstrates that changes in ligand efficacy can drive changes in GPCR specificity, thus obviating the need for extensive binding pocket re-modeling.
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Registered trials
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