+Search query
-Structure paper
Title | Cryo-EM structures of Gid12-bound GID E3 reveal steric blockade as a mechanism inhibiting substrate ubiquitylation. |
---|---|
Journal, issue, pages | Nat Commun, Vol. 13, Issue 1, Page 3041, Year 2022 |
Publish date | Jun 1, 2022 |
![]() | Shuai Qiao / Chia-Wei Lee / Dawafuti Sherpa / Jakub Chrustowicz / Jingdong Cheng / Maximilian Duennebacke / Barbara Steigenberger / Ozge Karayel / Duc Tung Vu / Susanne von Gronau / Matthias Mann / Florian Wilfling / Brenda A Schulman / ![]() ![]() ![]() |
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 ...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. |
![]() | ![]() ![]() ![]() |
Methods | EM (single particle) |
Resolution | 3.3 - 31.2 Å |
Structure data | ![]() EMDB-14323: Structure of Chelator-GIDSR4 bound to Mdh2 ![]() EMDB-14324: Structure of Cage-GIDSR4 bound to PHSVTP-Fbp1 ![]() EMDB-14338: Structure of endogenous Cage-GIDAnt complex EMDB-32830, PDB-7wug: ![]() EMDB-32831: Gid12 bound GIDSR4 E3 ubiquitin ligase complex ![]() EMDB-32833: Gid12 bound Chelator-GIDSR4 ![]() EMDB-32834: Cage assembly GID E3 ubiquitin ligase ![]() EMDB-32835: Gid12 bound Cage-GIDSR3 |
Source |
|
![]() | LIGASE / E3 ubiquitin Ligase / beta-propellor |