7NS3

Substrate receptor scaffolding module of yeast Chelator-GID SR4 E3 ubiquitin ligase bound to Fbp1 substrate

これはPDB形式変換不可エントリーです。

7NS3 の概要

• エントリーDOI: 10.2210/pdb7ns3/pdb
• EMDBエントリー: 12538 12540 12541 12548 12557 12559
• 分子名称: Vacuolar import and degradation protein 28, Glucose-induced degradation protein 8, BJ4_G0018240.mRNA.1.CDS.1, ... (6 entities in total)
• 機能のキーワード: gid, ctlh, ubiquitin, e3 ligase, supramolecular assembly, metabolism, gluconeogenesis, cryoem, ligase
• 由来する生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 409270.63

構造登録者

Sherpa, D.,Chrustowicz, J.,Prabu, J.R.,Schulman, B.A. (登録日: 2021-03-05, 公開日: 2021-05-05, 最終更新日: 2025-07-09)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.5 Å)