登録情報 データベース : EMDB / ID : EMD-12037 構造の表示 ダウンロードとリンクタイトル 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 マップデータTS1 SCF SKP2- Composite map 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.複合体 : Cullin-1, E3 ubiquitin-protein ligase RBX1リガンド : x 2種 詳細 キーワード ubiquitin / ubiquitin ligase / E3 ligase / F-box protein / RBR ligase / Cullin-RING-Ligase / CRL / SCF / NEDD8 / Post-translational modification / ubiquitylation / LIGASE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 / cyclin-dependent protein kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cyclin-dependent protein kinase activity / negative regulation of cardiac muscle tissue regeneration / negative regulation of kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / FOXO-mediated transcription of cell cycle genes ... PKR/eIFalpha signaling / cyclin-dependent protein kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cyclin-dependent protein kinase activity / negative regulation of cardiac muscle tissue regeneration / negative regulation of kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / autophagic cell death / FOXO-mediated transcription of cell cycle genes / cell cycle phase transition / Parkin-FBXW7-Cul1 ubiquitin ligase complex / Lewy body / ubiquitin-protein transferase activator activity / RBR-type E3 ubiquitin transferase / F-box domain binding / negative regulation of epithelial cell proliferation involved in prostate gland development / negative regulation of cyclin-dependent protein serine/threonine kinase activity / cellular response to cell-matrix adhesion / : / cyclin A2-CDK1 complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of cell cycle G1/S phase transition / PcG protein complex / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / regulation of exit from mitosis / cullin-RING-type E3 NEDD8 transferase / negative regulation of epithelial cell apoptotic process / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / epithelial cell proliferation involved in prostate gland development / positive regulation of ubiquitin protein ligase activity / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / ubiquitin ligase activator activity / regulation of cyclin-dependent protein serine/threonine kinase activity / RHO GTPases activate CIT / positive regulation of protein autoubiquitination / RNA polymerase II transcription initiation surveillance / protein neddylation / protein K11-linked ubiquitination / male pronucleus / cyclin-dependent protein serine/threonine kinase activator activity / nuclear export / female pronucleus / negative regulation of mitotic cell cycle / ubiquitin conjugating enzyme binding / Modulation of host responses by IFN-stimulated genes / NEDD8 ligase activity / cellular response to cocaine / AKT phosphorylates targets in the cytosol / VCB complex / epithelial cell apoptotic process / response to glucagon / negative regulation of response to oxidative stress / Cul5-RING ubiquitin ligase complex / positive regulation of protein targeting to mitochondrion / positive regulation of DNA biosynthetic process / cellular response to antibiotic / cyclin-dependent protein serine/threonine kinase regulator activity / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / cellular response to glucocorticoid stimulus / negative regulation of type I interferon production / ubiquitin-ubiquitin ligase activity / molecular function inhibitor activity / E2 ubiquitin-conjugating enzyme / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / cellular response to steroid hormone stimulus / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / cellular response to lithium ion / Cul3-RING ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / Cul4B-RING E3 ubiquitin ligase complex / cellular response to insulin-like growth factor stimulus / ubiquitin ligase complex scaffold activity / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / negative regulation of mitophagy / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / Prolactin receptor signaling / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / RSV-host interactions / X chromosome / Constitutive Signaling by AKT1 E17K in Cancer 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 / Cyclin-dependent kinase inhibitor domain / Cyclin-dependent kinase inhibitor domain superfamily / Cyclin-dependent kinase inhibitor / Cyclin-dependent kinase, regulatory subunit / Cyclin-dependent kinase, regulatory subunit superfamily ... : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / Cyclin-dependent kinase inhibitor domain / Cyclin-dependent kinase inhibitor domain superfamily / Cyclin-dependent kinase inhibitor / Cyclin-dependent kinase, regulatory subunit / Cyclin-dependent kinase, regulatory subunit superfamily / Cyclin-dependent kinase regulatory subunit / Cyclin-dependent kinases regulatory subunits signature 1. / Cyclin-dependent kinases regulatory subunits signature 2. / Cyclin-dependent kinase regulatory subunit / IBR domain, a half RING-finger domain / Nedd8-like ubiquitin / IBR domain / IBR domain / A Receptor for Ubiquitination Targets / In Between Ring fingers / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / TRIAD supradomain / F-box domain profile. / TRIAD supradomain profile. / F-box-like / F-box-like domain superfamily / SKP1 component, dimerisation / S-phase kinase-associated protein 1 / SKP1-like, dimerisation domain superfamily / Skp1 family, dimerisation domain / Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / F-box domain / : / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / : / Cyclin, C-terminal domain / : / Cyclins signature. / Cyclin / Cullin protein neddylation domain / : / Cullin, conserved site / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cyclin, C-terminal domain / Cyclin_C / Cullin / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin alpha solenoid domain / Cullin family profile. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Zinc finger, C3HC4 RING-type / Skp1 family, tetramerisation domain / Found in Skp1 protein family / Zinc finger, C3HC4 type (RING finger) / Cyclin, N-terminal / Cyclin, N-terminal domain / Ubiquitin-conjugating enzyme, active site / Ubiquitin-conjugating (UBC) active site signature. / Ubiquitin-conjugating enzyme E2 / Ubiquitin-conjugating enzyme / Ubiquitin-conjugating (UBC) core domain profile. / Ubiquitin-conjugating enzyme E2, catalytic domain homologues / Cyclin-like / domain present in cyclins, TFIIB and Retinoblastoma / Ubiquitin-conjugating enzyme/RWD-like / Cyclin-like superfamily / : / SKP1/BTB/POZ domain superfamily / Ring finger / Leucine-rich repeat domain superfamily / 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 / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Winged helix-like DNA-binding domain superfamily / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. 類似検索 - ドメイン・相同性 Polyubiquitin-C / Cyclin-A2 / Cyclin-dependent kinase 2 / Cyclin-dependent kinase inhibitor 1B / Cyclin-dependent kinases regulatory subunit 1 / E3 ubiquitin-protein ligase RBX1 / S-phase kinase-associated protein 1 / Ubiquitin-conjugating enzyme E2 L3 / S-phase kinase-associated protein 2 / Cullin-1 ... Polyubiquitin-C / Cyclin-A2 / Cyclin-dependent kinase 2 / Cyclin-dependent kinase inhibitor 1B / Cyclin-dependent kinases regulatory subunit 1 / E3 ubiquitin-protein ligase RBX1 / S-phase kinase-associated protein 1 / Ubiquitin-conjugating enzyme E2 L3 / S-phase kinase-associated protein 2 / Cullin-1 / Ubiquitin-like protein 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 : 3.8 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4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 2025年7月2日 - 現状 2025年7月2日 処理サイト : PDBe / 状態 : 公開
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