A GID E3 ligase assembly ubiquitinates an Rsp5 E3 adaptor and regulates plasma membrane transporters

• Published in: bioRxiv
• Main Authors: Langlois, Christine R, Beier, Viola, Karayel, Ozge, Chrustowicz, Jakub, Sherpa, Dawafuti, Mann, Matthias, Schulman, Brenda
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 02.09.2021; Cold Spring Harbor Laboratory
• Edition: 1.1
• Subjects: Cell Biology; Crystal structure; Environmental conditions; Gluconeogenesis; Glycolysis; Localization; Nutrient availability; Osmolarity; Proteomes; Ubiquitin; Ubiquitin-protein ligase; Rsp5; metabolism; GID; ubiquitin E3 ligase; nutrient signaling
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2021.09.02.458684

Cells rapidly remodel their proteomes to align their cellular metabolism to environmental conditions. Ubiquitin E3 ligases enable this response, by facilitating rapid and reversible changes to protein stability, localization, or interaction partners. In S. cerevisiae, the GID E3 ligase regulates the switch from gluconeogenic to glycolytic conditions through induction and incorporation of the substrate receptor subunit Gid4, which promotes the degradation of gluconeogenic enzymes. Here, we show an alternative substrate receptor, Gid10, which is induced in response to changes in temperature, osmolarity and nutrient availability, and regulates the ART-Rsp5 pathway. Art2 levels are elevated upon GID10 deletion, a crystal structure shows the basis for Gid10-Art2 interactions, and Gid10 directs a GID E3 ligase complex to ubiquitinate Art2. We also find that the GID E3 ligase affects the flux of plasma membrane nutrient transporters during heat stress. The data reveal GID as a system of E3 ligases with metabolic regulatory functions outside of glycolysis and gluconeogenesis, controlled by distinct stress-specific substrate receptors. Competing Interest Statement The authors have declared no competing interest.