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 cardiac muscle tissue regeneration / ubiquitin-like protein transferase activity / positive regulation of protein polyubiquitination / autophagic cell death / FOXO-mediated transcription of cell cycle genes / cell cycle phase transition / ubiquitin-protein transferase activator activity ... PKR/eIFalpha signaling / cyclin-dependent protein kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cardiac muscle tissue regeneration / ubiquitin-like protein transferase activity / positive regulation of protein polyubiquitination / autophagic cell death / FOXO-mediated transcription of cell cycle genes / cell cycle phase transition / ubiquitin-protein transferase activator activity / RBR-type E3 ubiquitin transferase / Parkin-FBXW7-Cul1 ubiquitin ligase complex / negative regulation of epithelial cell proliferation involved in prostate gland development / cellular response to cell-matrix adhesion / F-box domain binding / cyclin A2-CDK1 complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / regulation of cell cycle G1/S phase transition / cell cycle G1/S phase transition / cellular response to luteinizing hormone stimulus / PcG protein complex / epithelial cell proliferation involved in prostate gland development / G2/M DNA replication checkpoint / regulation of exit from mitosis / negative regulation of epithelial cell apoptotic process / negative regulation of beige fat cell differentiation / cyclin-dependent protein serine/threonine kinase inhibitor activity / cellular response to camptothecin / cullin-RING-type E3 NEDD8 transferase / NEDD8 transferase activity / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / cellular response to leptin stimulus / cullin-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Cul7-RING ubiquitin ligase complex / regulation of cyclin-dependent protein serine/threonine kinase activity / cellular response to chemical stress / RHO GTPases activate CIT / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / male pronucleus / nuclear export / female pronucleus / cyclin-dependent protein serine/threonine kinase activator activity / positive regulation of protein autoubiquitination / negative regulation of mitotic cell cycle / protein K11-linked ubiquitination / RNA polymerase II transcription initiation surveillance / epithelial cell apoptotic process / protein neddylation / cellular response to cocaine / Modulation of host responses by IFN-stimulated genes / AKT phosphorylates targets in the cytosol / response to glucagon / ubiquitin ligase activator activity / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / protein K27-linked ubiquitination / : / negative regulation of response to oxidative stress / cyclin-dependent protein serine/threonine kinase regulator activity / VCB complex / cellular response to glucocorticoid stimulus / molecular function inhibitor activity / Cul5-RING ubiquitin ligase complex / positive regulation of DNA biosynthetic process / ubiquitin-ubiquitin ligase activity / E2 ubiquitin-conjugating enzyme / cellular response to lithium ion / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / cellular response to steroid hormone stimulus / SCF ubiquitin ligase complex / positive regulation of intracellular estrogen receptor signaling pathway / Cul2-RING ubiquitin ligase complex / cyclin A1-CDK2 complex / cyclin E2-CDK2 complex / cyclin E1-CDK2 complex / cellular response to insulin-like growth factor stimulus / cyclin A2-CDK2 complex / positive regulation of DNA-templated DNA replication initiation / G2 Phase / Y chromosome / cyclin-dependent protein kinase activity / regulation of heterochromatin organization / Cul3-RING ubiquitin ligase complex / Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes / negative regulation of type I interferon production / positive regulation of heterochromatin formation / p53-Dependent G1 DNA Damage Response / X chromosome / PTK6 Regulates Cell Cycle / RSV-host interactions / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / Lewy body / Prolactin receptor signaling / Constitutive Signaling by AKT1 E17K in Cancer / negative regulation of mitophagy / regulation of anaphase-promoting complex-dependent catabolic process / Cul4B-RING E3 ubiquitin ligase complex 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 / In Between Ring fingers / TRIAD supradomain / TRIAD supradomain profile. / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / F-box domain profile. / Cyclin-A, N-terminal APC/C binding region / Cyclin-A N-terminal APC/C binding region / 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 / : / F-box domain / : / Cyclin, C-terminal domain / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / : / Cyclins signature. / Cyclin / Cyclin, C-terminal domain / Cyclin_C / Cullin, N-terminal / Cullin protein neddylation domain / : / Cullin, conserved site / Cullin alpha solenoid domain / Cullin family signature. / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / Cullin / : / Cullin alpha+beta domain / Cullin homology domain / Cullin homology domain superfamily / Cullin family profile. / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / S-phase kinase-associated protein 1-like / Cyclin, N-terminal / SKP1 component, POZ domain / Cyclin, N-terminal domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / 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 / : / Ring finger / SKP1/BTB/POZ domain superfamily / 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 / Serine/Threonine protein kinases, catalytic domain / Winged helix-like DNA-binding domain superfamily 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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