Year: 2023
Type: article
Abstract: Target of rapamycin complex 1 (TORC1) is a protein kinase controlling cell homeostasis and growth in response to nutrients and stresses. In Saccharomyces cerevisiae, glucose depletion triggers a redistribution of TORC1 from a dispersed localization over the vacuole surface into a large, inactive condensate called TOROID (TORC1 organized in inhibited domains). However, the mechanisms governing this transition have been unclear. Here, we show that acute depletion and repletion of EGO complex (EGOC) activity is sufficient to control TOROID distribution, independently of other nutrient-signaling pathways. The 3.9-Å-resolution structure of TORC1 from TOROID cryo-EM data together with interrogation of key interactions in vivo provide structural insights into TORC1-TORC1' and TORC1-EGOC interaction interfaces. These data support a model in which glucose-dependent activation of EGOC triggers binding to TORC1 at an interface required for TOROID assembly, preventing TORC1 polymerization and promoting release of active TORC1.
Institutions: University of Geneva, Ghent University, VIB-UGent Center for Inflammation Research, Centre National de la Recherche Scientifique, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, CEA Grenoble, Institut de Biologie Structurale, Université Grenoble Alpes, NCCR Chemical Biology - Visualisation and Control of Biological Processes Using Chemistry
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,690
Funders: National Science Foundation, European Molecular Biology Laboratory, Infrastructures en Biologie Santé et Agronomie, European Commission, Agence Nationale de la Recherche, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Fondation pour la Recherche Médicale, Vlaams Instituut voor Biotechnologie, Centre National de la Recherche Scientifique, Université de Genève, French Infrastructure for Integrated Structural Biology, Canton de Genève, Vlaamse regering, H2020 Marie Skłodowska-Curie Actions
Awards: G1183670895, CBH-EUR-GS, G1825864493, G2277544366, G2447855386, G256544642, G2659019386, G2911514573, Structural and functional insights into the assembly of respiratory complexes by a novel putative chaperone, G4285481387, G434337789, G4460985483, G6103885319, G6803667113, G6891474181, G7240651115, G7358480839, G796440745, G8305889996, Infrastructure Française pour la Biologie Structurale Intégrée
OpenAlex ID: W4318071652