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Publication Abstract from PubMed

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 GID(SR4) 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 (GID(Ant)), which awaits a glucose-induced substrate receptor to form the active GID(SR4). Meanwhile, other environmental perturbations elicit production of an alternative substrate receptor assembling into a related E3 ligase complex. The intricate structure of GID(Ant) enables anticipating and ultimately binding various N-degron-targeting (i.e., "N-end rule") substrate receptors, while the GID(SR4) 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.

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly.,Qiao S, Langlois CR, Chrustowicz J, Sherpa D, Karayel O, Hansen FM, Beier V, von Gronau S, Bollschweiler D, Schafer T, Alpi AF, Mann M, Prabu JR, Schulman BA Mol Cell. 2019 Nov 1. pii: S1097-2765(19)30769-5. doi:, 10.1016/j.molcel.2019.10.009. PMID:31708416^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.