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

Molecular Cell. 2020; 
Qiao S, Langlois CR, Chrustowicz J, Sherpa D, Karayel O, Hansen FM, Beier V, von Gronau S, Bollschweiler D, Schäfer T, Alpi AF, Mann M, Prabu JR, Schulman BA.
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摘要

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 pr... More

关键词

CTLH; E3 ligase; GID; N-degron; N-end rule; cryo-EM; gluconeogenesis; metabolism; stress response; ubiquitin