EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Non-canonical substrate recognition by the human WDR26-CTLH E3 ligase regulates prodrug metabolism.
ジャーナル・号・ページ	Mol Cell, Vol. 84, Issue 10, Page 1948-1963.e11, Year 2024
掲載日	2024年5月16日
著者	Karthik V Gottemukkala / Jakub Chrustowicz / Dawafuti Sherpa / Sara Sepic / Duc Tung Vu / Özge Karayel / Eleftheria C Papadopoulou / Annette Gross / Kenji Schorpp / Susanne von Gronau / Kamyar Hadian / Peter J Murray / Matthias Mann / Brenda A Schulman / Arno F Alpi /
PubMed 要旨	The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic ...The yeast glucose-induced degradation-deficient (GID) E3 ubiquitin ligase forms a suite of complexes with interchangeable receptors that selectively recruit N-terminal degron motifs of metabolic enzyme substrates. The orthologous higher eukaryotic C-terminal to LisH (CTLH) E3 complex has been proposed to also recognize substrates through an alternative subunit, WDR26, which promotes the formation of supramolecular CTLH E3 assemblies. Here, we discover that human WDR26 binds the metabolic enzyme nicotinamide/nicotinic-acid-mononucleotide-adenylyltransferase 1 (NMNAT1) and mediates its CTLH E3-dependent ubiquitylation independently of canonical GID/CTLH E3-family substrate receptors. The CTLH subunit YPEL5 inhibits NMNAT1 ubiquitylation and cellular turnover by WDR26-CTLH E3, thereby affecting NMNAT1-mediated metabolic activation and cytotoxicity of the prodrug tiazofurin. Cryoelectron microscopy (cryo-EM) structures of NMNAT1- and YPEL5-bound WDR26-CTLH E3 complexes reveal an internal basic degron motif of NMNAT1 essential for targeting by WDR26-CTLH E3 and degron mimicry by YPEL5's N terminus antagonizing substrate binding. Thus, our data provide a mechanistic understanding of how YPEL5-WDR26-CTLH E3 acts as a modulator of NMNAT1-dependent metabolism.
リンク	Mol Cell / PubMed:38759627 / PubMed Central
手法	EM (単粒子)
解像度	3.2 - 13.9 Å
構造データ	EMDB-18170: YPEL5-bound WDR26-CTLH E3 ligase - assembly I 手法: EM (単粒子) / 解像度: 8.9 Å EMDB-18171: YPEL5-bound WDR26-CTLH E3 ligase - assembly II 手法: EM (単粒子) / 解像度: 11.2 Å EMDB-18172: NMNAT1 core-bound RANBP9-TWA1-WDR26 module of WDR26-CTLH E3 ligase 手法: EM (単粒子) / 解像度: 4.7 Å EMDB-18173: NMNAT1 loop-bound RANBP9-TWA1-WDR26 module of WDR26-CTLH E3 ligase 手法: EM (単粒子) / 解像度: 8.7 Å EMDB-18174: NMNAT1-bound WDR26-CTLH E3 ligase assembly I - class 1 手法: EM (単粒子) / 解像度: 10.0 Å EMDB-18175: NMNAT1-bound WDR26-CTLH E3 ligase assembly I - class 2 手法: EM (単粒子) / 解像度: 10.3 Å EMDB-18176: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 1 手法: EM (単粒子) / 解像度: 11.5 Å EMDB-18177: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 2 手法: EM (単粒子) / 解像度: 13.9 Å EMDB-18178: NMNAT1-bound WDR26-CTLH E3 ligase assembly II - class 3 手法: EM (単粒子) / 解像度: 12.2 Å 18316 8qbn EMDB-18316, PDB-8qbn: Structure of the non-canonical CTLH E3 substrate receptor WDR26 bound to YPEL5 手法: EM (単粒子) / 解像度: 3.2 Å 18345 8qe8 EMDB-18345, PDB-8qe8: Structure of the non-canonical CTLH E3 substrate receptor WDR26 bound to NMNAT1 substrate 手法: EM (単粒子) / 解像度: 3.8 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-NMN: BETA-NICOTINAMIDE RIBOSE MONOPHOSPHATE / ニコチンアミドモノヌクレオチド
由来	homo sapiens (ヒト)
キーワード	LIGASE / E3 ubiquitin ligase / CTLH / GID / NMNAT1 / YPEL5 / NAD / NADH