Forskning ved Københavns Universitet - Københavns Universitet


Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Shuai Qiao
  • Christine R Langlois
  • Jakub Chrustowicz
  • Dawafuti Sherpa
  • Ozge Karayel
  • Fynn M Hansen
  • Viola Beier
  • Susanne von Gronau
  • Daniel Bollschweiler
  • Tillman Schäfer
  • Arno F Alpi
  • Mann, Matthias
  • J Rajan Prabu
  • Brenda A Schulman

Cells respond to environmental changes by toggling metabolic pathways, preparing for homeostasis, and anticipating future stresses. For example, in Saccharomyces cerevisiae, carbon stress-induced gluconeogenesis is terminated upon glucose availability, a process that involves the multiprotein E3 ligase GIDSR4 recruiting N termini and catalyzing ubiquitylation of gluconeogenic enzymes. Here, genetics, biochemistry, and cryoelectron microscopy define molecular underpinnings of glucose-induced degradation. Unexpectedly, carbon stress induces an inactive anticipatory complex (GIDAnt), which awaits a glucose-induced substrate receptor to form the active GIDSR4. Meanwhile, other environmental perturbations elicit production of an alternative substrate receptor assembling into a related E3 ligase complex. The intricate structure of GIDAnt enables anticipating and ultimately binding various N-degron-targeting (i.e., "N-end rule") substrate receptors, while the GIDSR4 E3 forms a clamp-like structure juxtaposing substrate lysines with the ubiquitylation active site. The data reveal evolutionarily conserved GID complexes as a family of multisubunit E3 ubiquitin ligases responsive to extracellular stimuli.

TidsskriftMolecular Cell
StatusE-pub ahead of print - 1 nov. 2019
Eksternt udgivetJa

ID: 230143911