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TitleEGOC inhibits TOROID polymerization by structurally activating TORC1.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 3, Page 273-285, Year 2023
Publish dateJan 26, 2023
AuthorsManoël Prouteau / Clélia Bourgoint / Jan Felix / Lenny Bonadei / Yashar Sadian / Caroline Gabus / Savvas N Savvides / Irina Gutsche / Ambroise Desfosses / Robbie Loewith /
PubMed AbstractTarget 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 ...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.
External linksNat Struct Mol Biol / PubMed:36702972 / PubMed Central
MethodsEM (single particle) / EM (helical sym.)
Resolution3.87 - 9.1 Å
Structure data

EMDB-13594, PDB-7pqh:
Cryo-EM structure of Saccharomyces cerevisiae TOROID (TORC1 Organized in Inhibited Domains).
Method: EM (single particle) / Resolution: 3.87 Å

EMDB-13595: Helical reconstruction of TOROID (TORC1 Organized in Inhibited Domains) filaments.
Method: EM (helical sym.) / Resolution: 9.1 Å

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsSIGNALING PROTEIN / TARGET OF RAPAMYCIN / TORC1 / KOG1 / LST8 / TOR2 / FRB DOMAIN

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