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

Shuai Qiao, Christine R Langlois, Jakub Chrustowicz, Dawafuti Sherpa, Ozge Karayel, Fynn M Hansen, Viola Beier, Susanne von Gronau, Daniel Bollschweiler, Tillman Schafer, Arno F Alpi, Matthias Mann (+2 others)
2019 bioRxiv   pre-print
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 cryo electron microscopy define molecular underpinnings of glucose-induced
more » ... egradation. 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.
doi:10.1101/824060 fatcat:r3gkbtm3ovggnerzmkf3igwdt4