7NS4

Catalytic module of yeast Chelator-GID SR4 E3 ubiquitin ligase

Summary for 7NS4

• Entry DOI: 10.2210/pdb7ns4/pdb
• Related: 7NS3
• EMDB information: 12538 12540 12541 12548 12557 12559 12560
• Descriptor: E3 ubiquitin-protein ligase RMD5, Protein FYV10, ZINC ION (3 entities in total)
• Functional Keywords: gid, ctlh, ubiquitin, e3 ligase, supramolecular assembly, metabolism, gluconeogenesis, cryoem, ligase
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 109350.51

Authors

Sherpa, D.,Chrustowicz, J.,Prabu, J.R.,Schulman, B.A. (deposition date: 2021-03-05, release date: 2021-05-05, Last modification date: 2024-07-10)

Primary citation

Sherpa, D.,Chrustowicz, J.,Qiao, S.,Langlois, C.R.,Hehl, L.A.,Gottemukkala, K.V.,Hansen, F.M.,Karayel, O.,von Gronau, S.,Prabu, J.R.,Mann, M.,Alpi, A.F.,Schulman, B.A.
GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme.
Mol.Cell, 81:2445-, 2021

PubMed Abstract: How are E3 ubiquitin ligases configured to match substrate quaternary structures? Here, by studying the yeast GID complex (mutation of which causes deficiency in glucose-induced degradation of gluconeogenic enzymes), we discover supramolecular chelate assembly as an E3 ligase strategy for targeting an oligomeric substrate. Cryoelectron microscopy (cryo-EM) structures show that, to bind the tetrameric substrate fructose-1,6-bisphosphatase (Fbp1), two minimally functional GID E3s assemble into the 20-protein Chelator-GID, which resembles an organometallic supramolecular chelate. The Chelator-GID assembly avidly binds multiple Fbp1 degrons so that multiple Fbp1 protomers are simultaneously ubiquitylated at lysines near the allosteric and substrate binding sites. Importantly, key structural and biochemical features, including capacity for supramolecular assembly, are preserved in the human ortholog, the CTLH E3. Based on our integrative structural, biochemical, and cell biological data, we propose that higher-order E3 ligase assembly generally enables multipronged targeting, capable of simultaneously incapacitating multiple protomers and functionalities of oligomeric substrates.

PubMed: 33905682
DOI: 10.1016/j.molcel.2021.03.025

Experimental method

ELECTRON MICROSCOPY (3.9 Å)