登録情報 データベース : EMDB / ID : EMD-12050 構造の表示 ダウンロードとリンクタイトル 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 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 : 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 : E3 ubiquitin-protein ligase ARIH1タンパク質・ペプチド : E3 ubiquitin-protein ligase ARIH1リガンド : ZINC ION 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 / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / Cul7-RING ubiquitin ligase complex ... PKR/eIFalpha signaling / ubiquitin-like protein transferase activity / Lewy body / Parkin-FBXW7-Cul1 ubiquitin ligase complex / RBR-type E3 ubiquitin transferase / 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 / positive regulation of protein autoubiquitination / protein neddylation / ubiquitin conjugating enzyme binding / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / Cul2-RING ubiquitin ligase complex / Cajal body / 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 / RSV-host interactions / Prolactin receptor signaling / protein monoubiquitination / cullin family protein binding / protein K48-linked ubiquitination / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / ubiquitin ligase complex / positive regulation of TORC1 signaling / T cell activation / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / MAP3K8 (TPL2)-dependent MAPK1/3 activation / cellular response to amino acid stimulus / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Degradation of DVL / Dectin-1 mediated noncanonical NF-kB signaling / SCF(Skp2)-mediated degradation of p27/p21 / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / animal organ morphogenesis / Activation of NF-kappaB in B cells / Negative regulation of NOTCH4 signaling / Iron uptake and transport / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Vif-mediated degradation of APOBEC3G / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / DNA Damage Recognition in GG-NER / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / PKR-mediated signaling / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Cyclin D associated events in G1 / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / G1/S transition of mitotic cell cycle / Formation of TC-NER Pre-Incision Complex / Dual Incision in GG-NER / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / ISG15 antiviral mechanism / CLEC7A (Dectin-1) signaling / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / Regulation of expression of SLITs and ROBOs / Formation of Incision Complex in GG-NER / FCERI mediated NF-kB activation / Dual incision in TC-NER / Interleukin-1 signaling / Gap-filling DNA repair synthesis and ligation in TC-NER / Regulation of RAS by GAPs / protein polyubiquitination / positive regulation of protein catabolic process / ubiquitin-protein transferase activity / Regulation of RUNX2 expression and activity / cellular response to UV / MAPK cascade / Regulation of PLK1 Activity at G2/M Transition / ubiquitin protein ligase activity / KEAP1-NFE2L2 pathway / Circadian Clock / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / Neddylation / protein-macromolecule adaptor activity 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 / IBR domain, a half RING-finger domain / IBR domain / In Between Ring fingers / TRIAD supradomain / TRIAD supradomain profile. ... : / E3 ubiquitin-protein ligase ARIH1, UBA-like domain / Ariadne domain / Ariadne domain / E3 ubiquitin ligase RBR family / 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) / Ring finger / Zinc finger RING-type profile. / Zinc finger, RING-type / Zinc finger, RING/FYVE/PHD-type / Winged helix DNA-binding domain superfamily / Winged helix-like DNA-binding domain superfamily 類似検索 - ドメイン・相同性 E3 ubiquitin-protein ligase RBX1 / 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 : 3.6 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7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 2024年5月1日 - 現状 2024年5月1日 処理サイト : PDBe / 状態 : 公開
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