7WUG

GID subcomplex: Gid12 bound Substrate Receptor Scaffolding module

Summary for 7WUG

• Entry DOI: 10.2210/pdb7wug/pdb
• EMDB information: 32830
• Descriptor: Vacuolar import and degradation protein 28, Glucose-induced degradation protein 8, Vacuolar import and degradation protein 30, ... (5 entities in total)
• Functional Keywords: e3 ubiquitin ligase, beta-propellor, ligase
• Biological source: Saccharomyces cerevisiae YJM1133; More
• Total number of polymer chains: 5
• Total formula weight: 388591.55

Authors

Qiao, S.,Cheng, J.D.,Schulman, B.A. (deposition date: 2022-02-08, release date: 2022-06-08, Last modification date: 2025-06-18)

Primary citation

Qiao, S.,Lee, C.W.,Sherpa, D.,Chrustowicz, J.,Cheng, J.,Duennebacke, M.,Steigenberger, B.,Karayel, O.,Vu, D.T.,von Gronau, S.,Mann, M.,Wilfling, F.,Schulman, B.A.
Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation.
Nat Commun, 13:3041-3041, 2022

PubMed Abstract: Protein degradation, a major eukaryotic response to cellular signals, is subject to numerous layers of regulation. In yeast, the evolutionarily conserved GID E3 ligase mediates glucose-induced degradation of fructose-1,6-bisphosphatase (Fbp1), malate dehydrogenase (Mdh2), and other gluconeogenic enzymes. "GID" is a collection of E3 ligase complexes; a core scaffold, RING-type catalytic core, and a supramolecular assembly module together with interchangeable substrate receptors select targets for ubiquitylation. However, knowledge of additional cellular factors directly regulating GID-type E3s remains rudimentary. Here, we structurally and biochemically characterize Gid12 as a modulator of the GID E3 ligase complex. Our collection of cryo-EM reconstructions shows that Gid12 forms an extensive interface sealing the substrate receptor Gid4 onto the scaffold, and remodeling the degron binding site. Gid12 also sterically blocks a recruited Fbp1 or Mdh2 from the ubiquitylation active sites. Our analysis of the role of Gid12 establishes principles that may more generally underlie E3 ligase regulation.

PubMed: 35650207
DOI: 10.1038/s41467-022-30803-9

Experimental method

ELECTRON MICROSCOPY (3.3 Å)