登録情報 データベース : EMDB / ID : EMD-12041 構造の表示 ダウンロードとリンクタイトル Focused map-catalytic side. Ubiquitin ligation to F-box protein substrates by SCF-RBR E3-E3 super-assembly: NEDD8-CUL1-RBX1-UBE2L3~Ub~ARIH1. マップデータ 詳細 試料複合体 : NEDD8-CUL1-RBX1-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1 composite map.複合体 : NEDD8-SKP1-SKP2-CKSHS1-Cyclin A-CDK2-p27-UBE2L3~Ub~ARIH1. Transition State 1 composite map.タンパク質・ペプチド : E3 ubiquitin-protein ligase ARIH1タンパク質・ペプチド : Polyubiquitin-Cタンパク質・ペプチド : NEDD8タンパク質・ペプチド : Ubiquitin-conjugating enzyme E2 L3複合体 : CUL1, RBX1タンパク質・ペプチド : Cullin-1タンパク質・ペプチド : E3 ubiquitin-protein ligase RBX1リガンド : ZINC IONリガンド : 5-azanylpentan-2-one 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cell cycle phase transition / RBR-type E3 ubiquitin transferase / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity ... PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / cell cycle phase transition / RBR-type E3 ubiquitin transferase / ubiquitin-protein transferase activator activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / protein K11-linked ubiquitination / regulation of proteolysis / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / cellular response to glucocorticoid stimulus / NEDD8 ligase activity / positive regulation of ubiquitin-protein transferase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / positive regulation of protein targeting to mitochondrion / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / negative regulation of type I interferon production / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / E2 ubiquitin-conjugating enzyme / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / cellular response to steroid hormone stimulus / RSV-host interactions / Prolactin receptor signaling / TGF-beta receptor signaling activates SMADs / protein monoubiquitination / ubiquitin conjugating enzyme activity / cullin family protein binding / anatomical structure morphogenesis / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / Cajal body / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / positive regulation of TORC1 signaling / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / T cell activation / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / NRIF signals cell death from the nucleus / Regulation of PTEN localization / Activated NOTCH1 Transmits Signal to the Nucleus / Regulation of BACH1 activity / Translesion synthesis by REV1 / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / intrinsic apoptotic signaling pathway / Translesion synthesis by POLK / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / post-translational protein modification / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation 類似検索 - 分子機能 : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / Nedd8-like ubiquitin / IBR domain, a half RING-finger domain / IBR domain / In Between Ring fingers / TRIAD supradomain ... : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / Nedd8-like ubiquitin / IBR domain, a half RING-finger domain / IBR domain / In Between Ring fingers / TRIAD supradomain / TRIAD supradomain profile. / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / Cullin protein neddylation domain / Cullin, conserved site / Cullin family signature. / Cullin / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin protein neddylation domain / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme/RWD-like / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Zinc finger, RING/FYVE/PHD-type / Ubiquitin-like domain superfamily / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 Polyubiquitin-C / E3 ubiquitin-protein ligase RBX1 / Ubiquitin-conjugating enzyme E2 L3 / Cullin-1 / NEDD8 / E3 ubiquitin-protein ligase ARIH1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.6 Å 詳細 データ登録者Horn-Ghetko D / Prabu JR / Schulman BA 資金援助 ドイツ, 2件 詳細 詳細を隠すOrganization Grant number 国 European Research Council (ERC) H2020 789016-NEDD8Activate ドイツ German Research Foundation (DFG) SCHU 3196/1-1 ドイツ
引用ジャーナル : Nature / 年 : 2021タイトル : Ubiquitin ligation to F-box protein targets by SCF-RBR E3-E3 super-assembly.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 / 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. 履歴 登録 2020年12月5日 - ヘッダ(付随情報) 公開 2021年2月10日 - マップ公開 2021年2月10日 - 更新 2021年3月10日 - 現状 2021年3月10日 処理サイト : PDBe / 状態 : 公開
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