On Sulfur Sensing in Saccharomyces cerevisiae

dc.contributor.advisorNijhawan, Deepaken
dc.contributor.committeeMemberDe Martino, Georgeen
dc.contributor.committeeMemberYu, Hongtaoen
dc.contributor.committeeMemberTu, Benjaminen
dc.creatorJohnson, Zane Milleren
dc.creator.orcid0000-0002-9497-8100
dc.date.accessioned2024-01-11T20:23:22Z
dc.date.available2024-01-11T20:23:22Z
dc.date.created2021-12
dc.date.issuedDecember 2021
dc.date.submittedDecember 2021
dc.date.updated2024-01-11T20:23:22Z
dc.description.abstractThe unique chemistry available to sulfur compared to oxygen, such as the ability to exist in numerous oxidation states and greater nucleophilicity, makes many of the biochemical reactions requisite for cellular life possible. As a result of this critical importance, organisms have developed several mechanisms for sensing and maintaining levels of sulfur-containing metabolites. In the yeast Saccharomyces cerevisiae, regulation of sulfur metabolism can be distilled down to the actions of two proteins; the F-box protein Met30, and the transcriptional coactivator Met4. Met30 belongs to the family of SCF (Skp1-Cul1-F-box protein) E3 ubiquitin ligases, and negatively regulates the transcriptional activity of the master transcriptional activator of sulfur metabolism genes, Met4, via oligo-ubiquitination when sulfur metabolite levels are high. When yeast are starved of sulfur, Met30 ceases to ubiquitinate Met4, releasing it to be deubiquitinated and transcriptionally active to boost levels of a network of sulfur metabolic genes known as the MET regulon to restore sulfur metabolite levels. While the molecular activities of both Met30 and Met4 have been extensively studied over the last two decades, the biochemical basis for sulfur-sensing by the Met30 E3 ligase has remained unknown. Herein, I reveal the biochemical details by which Met30, the master regulator of sulfur metabolism, senses the availability of sulfur metabolites to modulate its E3 ligase activity to regulate sulfur metabolism in yeast. Utilizing a combination of yeast genetics and biochemical assays, I show that Met30 uses redox-active cysteine residues in its C-terminal WD-40 repeat region to modulate binding between itself and its substrate Met4 in accordance with the availability of sulfur metabolites. These insights represent significant advances in the understanding of sulfur metabolic regulation in yeast.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1417098561
dc.identifier.urihttps://hdl.handle.net/2152.5/10244
dc.language.isoenen
dc.subjectCell Cycle Proteinsen
dc.subjectSaccharomyces cerevisiae Proteinsen
dc.subjectSaccharomyces cerevisiaeen
dc.subjectSulfuren
dc.titleOn Sulfur Sensing in Saccharomyces cerevisiaeen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineBiological Chemistryen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen
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