期刊
MOLECULAR CELL
卷 77, 期 1, 页码 150-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.10.009
关键词
-
资金
- Max Planck Society
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.
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