Quantification of mutation-derived bias for alternate mating functionalities of the Saccharomyces cerevisiae Ste2p pheromone receptor

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DOIResolve DOI: https://doi.org/10.1093/jb/mvv072
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  1. National Research Council of Canada. Aquatic and Crop Resource Development
FormatText, Article
Journal titleJournal of Biochemistry
ISSN0021-924X
1756-2651
Volume159
Issue1
Pages49–58
SubjectAlternate functionalities; G-protein-coupled receptor; Pheromone mating; Site-directed mutagenesis; Yeast
Abstract
Although well documented for mammalian G-protein-coupled receptors, alternate functionalities and associated alternate signalling remain to be unequivocally established for the Saccharomyces cerevisiae pheromone Ste2p receptor. Here, evidence supporting alternate functionalities for Ste2p is re-evaluated, extended and quantified. In particular, strong mating and constitutive signalling mutations, focusing on residues S254, P258 and S259 in TM6 of Ste2p, are stacked and investigated in terms of their effects on classical G-protein-mediated signal transduction associated with cell cycle arrest, and alternatively, their impact on downstream mating projection and zygote formation events. In relative dose response experiments, accounting for systemic and observational bias, mutational-derived functional differences were observed, validating the S254L-derived bias for downstream mating responses and highlighting complex relationships between TM6-mutation derived constitutive signalling and ligand-induced functionalities. Mechanistically, localization studies suggest that alterations to receptor trafficking may contribute to mutational bias, in addition to expected receptor conformational stabilization effects. Overall, these results extend previous observations and quantify the contributions of Ste2p variants to mediating cell cycle arrest versus downstream mating functionalities.
Publication date
PublisherOxford University Press
LanguageEnglish
Peer reviewedYes
NRC numberNRC-ACRD-65058
NPARC number23000379
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Record identifier2f030195-558a-4648-b715-5a825eca361d
Record created2016-07-12
Record modified2020-06-02
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