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	Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly.
ジャーナル・号・ページ	Nature, Vol. 590, Issue 7847, Page 671-676, Year 2021
掲載日	2021年2月3日
著者	Daniel Horn-Ghetko / David T Krist / J Rajan Prabu / Kheewoong Baek / Monique P C Mulder / Maren Klügel / Daniel C Scott / Huib Ovaa / Gary Kleiger / Brenda A Schulman /
PubMed 要旨	E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather ...E3 ligases are typically classified by hallmark domains such as RING and RBR, which are thought to specify unique catalytic mechanisms of ubiquitin transfer to recruited substrates. However, rather than functioning individually, many neddylated cullin-RING E3 ligases (CRLs) and RBR-type E3 ligases in the ARIH family-which together account for nearly half of all ubiquitin ligases in humans-form E3-E3 super-assemblies. Here, by studying CRLs in the SKP1-CUL1-F-box (SCF) family, we show how neddylated SCF ligases and ARIH1 (an RBR-type E3 ligase) co-evolved to ubiquitylate diverse substrates presented on various F-box proteins. We developed activity-based chemical probes that enabled cryo-electron microscopy visualization of steps in E3-E3 ubiquitylation, initiating with ubiquitin linked to the E2 enzyme UBE2L3, then transferred to the catalytic cysteine of ARIH1, and culminating in ubiquitin linkage to a substrate bound to the SCF E3 ligase. The E3-E3 mechanism places the ubiquitin-linked active site of ARIH1 adjacent to substrates bound to F-box proteins (for example, substrates with folded structures or limited length) that are incompatible with previously described conventional RING E3-only mechanisms. The versatile E3-E3 super-assembly may therefore underlie widespread ubiquitylation.
リンク	Nature / PubMed:33536622 / PubMed Central
手法	EM (単粒子)
解像度	3.6 - 9.7 Å
構造データ	EMDB-12004: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 ligase superassembly. NEDD8-CUL1-RBX1-SKP1-FBXW7-Cyclin E-ARIH1-UBE2L3~Ub. Pre-Transition State 1 手法: EM (単粒子) / 解像度: 4.5 Å EMDB-12005: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-FBXW7-Cyclin E-ARIH1~Ub. post-Transition State 1 手法: EM (単粒子) / 解像度: 8.09 Å EMDB-12006: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-SKP1-FBXW7-Cyclin E~Ub~ARIH1. Transition State 2 手法: EM (単粒子) / 解像度: 3.62 Å EMDB-12036: Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly 手法: EM (単粒子) / 解像度: 9.7 Å 12037 7b5l EMDB-12037, PDB-7b5l: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1 手法: EM (単粒子) / 解像度: 3.8 Å EMDB-12038: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1 手法: EM (単粒子) / 解像度: 3.83 Å EMDB-12039: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-SKP1-FBXW7-Cyclin E~Ub~ARIH1. Transition State 2 手法: EM (単粒子) / 解像度: 4.48 Å 12040 7b5m EMDB-12040, PDB-7b5m: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1. Transition State 2 手法: EM (単粒子) / 解像度: 3.91 Å 12041 7b5n EMDB-12041: Focused map-catalytic side. Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. PDB-7b5n: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. 手法: EM (単粒子) / 解像度: 3.6 Å 12048 7b5r EMDB-12048: Focused map- CyclinA-CDK2-class. Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27. Transition State 1 PDB-7b5r: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27 手法: EM (単粒子) / 解像度: 3.8 Å 12050 7b5s EMDB-12050: Focused map- Cullin scaffold. Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-ARIH1 Ariadne. Transition State 1 PDB-7b5s: Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: CUL1-RBX1-ARIH1 Ariadne. Transition State 1 手法: EM (単粒子) / 解像度: 3.6 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-SY8: 5-azanylpentan-2-one
由来	homo sapiens (ヒト)
キーワード	LIGASE (リガーゼ) / ubiquitin (ユビキチン) / ubiquitin ligase (ユビキチンリガーゼ) / E3 ligase (ユビキチンリガーゼ) / F-box protein (Fボックスタンパク質) / RBR ligase / Cullin-RING-Ligase / CRL / SCF / NEDD8 / Post-translational modification (翻訳後修飾) / ubiquitylation (ユビキチン)