登録情報 データベース : EMDB / ID : EMD-12040 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: CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1. Transition State 2 マップデータ 詳細 試料複合体 : CUL1-RBX1-SKP1-SKP2-CKSHS1-p27~Ub~ARIH1複合体 : Cullin-1, E3 ubiquitin-protein ligase 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複合体 : ARIH1, SKP2, CKS1B, SKP1, UBCタンパク質・ペプチド : E3 ubiquitin-protein ligase ARIH1タンパク質・ペプチド : S-phase kinase-associated protein 2タンパク質・ペプチド : Cyclin-dependent kinases regulatory subunit 1タンパク質・ペプチド : S-phase kinase-associated protein 1タンパク質・ペプチド : Polyubiquitin-C複合体 : Cyclin-dependent kinase inhibitor 1Bタンパク質・ペプチド : Cyclin-dependent kinase inhibitor 1Bリガンド : ZINC ION 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 / cyclin-dependent protein kinase activating kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / PTK6 Regulates Cell Cycle / Lewy body / autophagic cell death ... PKR/eIFalpha signaling / cyclin-dependent protein kinase activating kinase regulator activity / regulation of lens fiber cell differentiation / negative regulation of cardiac muscle tissue regeneration / negative regulation of cyclin-dependent protein kinase activity / positive regulation of protein polyubiquitination / ubiquitin-like protein transferase activity / PTK6 Regulates Cell Cycle / Lewy body / autophagic cell death / Parkin-FBXW7-Cul1 ubiquitin ligase complex / FOXO-mediated transcription of cell cycle genes / negative regulation of epithelial cell proliferation involved in prostate gland development / F-box domain binding / RBR-type E3 ubiquitin transferase / Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) / PcG protein complex / Aberrant regulation of mitotic exit in cancer due to RB1 defects / p53-Dependent G1 DNA Damage Response / regulation of cell cycle G1/S phase transition / regulation of exit from mitosis / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / mitotic cell cycle phase transition / cullin-RING ubiquitin ligase complex / epithelial cell proliferation involved in prostate gland development / negative regulation of epithelial cell apoptotic process / negative regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of phosphorylation / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / positive regulation of ubiquitin protein ligase activity / ubiquitin ligase activator activity / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / maintenance of protein location in nucleus / cyclin-dependent protein serine/threonine kinase inhibitor activity / positive regulation of protein autoubiquitination / negative regulation of vascular associated smooth muscle cell proliferation / protein neddylation / RHO GTPases activate CIT / cyclin-dependent protein serine/threonine kinase activator activity / nuclear export / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / negative regulation of mitotic cell cycle / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / AKT phosphorylates targets in the cytosol / positive regulation of intracellular estrogen receptor signaling pathway / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / epithelial cell apoptotic process / SCF ubiquitin ligase complex / cellular response to antibiotic / Cul2-RING ubiquitin ligase complex / Cajal body / Cyclin E associated events during G1/S transition / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / ubiquitin ligase complex scaffold activity / Cul4B-RING E3 ubiquitin ligase complex / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / negative regulation of kinase activity / molecular function inhibitor activity / regulation of cyclin-dependent protein serine/threonine kinase activity / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / cellular response to lithium ion / RSV-host interactions / positive regulation of DNA replication / protein kinase inhibitor activity / Prolactin receptor signaling / Cyclin A:Cdk2-associated events at S phase entry / cyclin-dependent protein kinase holoenzyme complex / protein monoubiquitination / Constitutive Signaling by AKT1 E17K in Cancer / regulation of mitotic cell cycle / regulation of G1/S transition of mitotic cell cycle / cullin family protein binding / inner ear development / protein K63-linked ubiquitination / cellular response to organic cyclic compound / cyclin binding / ubiquitin-like ligase-substrate adaptor activity / positive regulation of double-strand break repair via homologous recombination / response to amino acid / protein K48-linked ubiquitination / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / response to glucose / regulation of cellular response to insulin stimulus / response to cadmium ion / ubiquitin ligase complex / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Notch signaling pathway / Myoclonic epilepsy of Lafora / positive regulation of microtubule polymerization 類似検索 - 分子機能 : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / 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 ... : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / 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 / E3 ubiquitin ligase RBR family / IBR domain, a half RING-finger domain / Leucine-rich repeat, cysteine-containing subtype / Leucine-rich repeat - CC (cysteine-containing) subfamily / A Receptor for Ubiquitination Targets / IBR domain / In Between Ring fingers / F-box domain profile. / TRIAD supradomain / TRIAD supradomain profile. / F-box-like domain superfamily / F-box-like / SKP1 component, dimerisation / S-phase kinase-associated protein 1 / SKP1-like, dimerisation domain superfamily / Skp1 family, dimerisation domain / F-box domain / 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. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / Zinc finger, C3HC4 RING-type / Zinc finger, C3HC4 type (RING finger) / 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 / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 Polyubiquitin-C / Cyclin-dependent kinase inhibitor 1B / Cyclin-dependent kinases regulatory subunit 1 / E3 ubiquitin-protein ligase RBX1 / S-phase kinase-associated protein 1 / S-phase kinase-associated protein 2 / Cullin-1 / 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 : 3.91 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17日 - マップ公開 2021年2月17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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