登録情報 データベース : EMDB / ID : EMD-4739 構造の表示 ダウンロードとリンクタイトル Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome マップデータ 詳細 試料複合体 : Ternary complex of COP9 signalosome (CSN) and neddylated Cullin-Ring E3 ligase CRL (cullin-2 with Rbx1, Elongin-B, Elongin-C and VHL) 詳細 キーワード Cullin-Ring E3 Ligase COP9 signalosome neddylation / 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
COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / protein deneddylation / regulation of protein neddylation / eukaryotic translation initiation factor 3 complex ... COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / exosomal secretion / GTPase inhibitor activity / deNEDDylase activity / protein deneddylation / regulation of protein neddylation / eukaryotic translation initiation factor 3 complex / regulation of cellular response to hypoxia / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / RHOBTB3 ATPase cycle / NEDD8 transferase activity / COP9 signalosome / negative regulation of receptor signaling pathway via JAK-STAT / cullin-RING ubiquitin ligase complex / cellular response to chemical stress / Cul7-RING ubiquitin ligase complex / ubiquitin-dependent protein catabolic process via the C-end degron rule pathway / target-directed miRNA degradation / transcription elongation factor activity / VCB complex / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / elongin complex / positive regulation of protein autoubiquitination / protein neddylation / regulation of JNK cascade / Replication of the SARS-CoV-1 genome / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / metal-dependent deubiquitinase activity / NEDD8 ligase activity / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / Cul5-RING ubiquitin ligase complex / regulation of DNA damage response, signal transduction by p53 class mediator / SCF ubiquitin ligase complex / inner cell mass cell proliferation / intracellular membraneless organelle / Cul2-RING ubiquitin ligase complex / Cul4A-RING E3 ubiquitin ligase complex / ubiquitin-ubiquitin ligase activity / negative regulation of type I interferon production / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / Cul3-RING ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / SUMOylation of ubiquitinylation proteins / negative regulation of mitophagy / Prolactin receptor signaling / skeletal muscle cell differentiation / TGF-beta receptor signaling activates SMADs / negative regulation of transcription elongation by RNA polymerase II / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / regulation of postsynapse assembly / regulation of proteolysis / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / response to light stimulus / anatomical structure morphogenesis / protein monoubiquitination / Tat-mediated elongation of the HIV-1 transcript / ubiquitin-like ligase-substrate adaptor activity / Formation of HIV-1 elongation complex containing HIV-1 Tat / negative regulation of signal transduction / Formation of HIV elongation complex in the absence of HIV Tat / protein K48-linked ubiquitination / RNA Polymerase II Transcription Elongation / Nuclear events stimulated by ALK signaling in cancer / Formation of RNA Pol II elongation complex / JNK cascade / negative regulation of TORC1 signaling / protein serine/threonine kinase binding / RNA Polymerase II Pre-transcription Events / translation initiation factor activity / regulation of cellular response to insulin stimulus / positive regulation of TORC1 signaling / negative regulation of insulin receptor signaling pathway / post-translational protein modification / negative regulation of autophagy / intrinsic apoptotic signaling pathway / T cell activation / positive regulation of DNA-binding transcription factor activity / Regulation of BACH1 activity / transcription corepressor binding / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / cellular response to amino acid stimulus / Degradation of DVL / transcription elongation by RNA polymerase II / Degradation of GLI1 by the proteasome / Recognition of DNA damage by PCNA-containing replication complex / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / negative regulation of canonical Wnt signaling pathway / Iron uptake and transport / Negative regulation of NOTCH4 signaling 類似検索 - 分子機能 COP9 signalosome, subunit CSN8 / COP9 signalosome complex subunit 7, helix I / : / : / COP9 signalosome complex subunit 7a helix I domain / COP9 signalosome complex subunit 3-like, C-terminal helix / CSN7 helical bundle subdomain / COP9 signalosome complex subunit 3, N-terminal helical repeats / COP9 signalosome subunit 6 / : ... COP9 signalosome, subunit CSN8 / COP9 signalosome complex subunit 7, helix I / : / : / COP9 signalosome complex subunit 7a helix I domain / COP9 signalosome complex subunit 3-like, C-terminal helix / CSN7 helical bundle subdomain / COP9 signalosome complex subunit 3, N-terminal helical repeats / COP9 signalosome subunit 6 / : / COP9 signalosome complex subunit 1, C-terminal helix / Cop9 signalosome subunit 5 C-terminal domain / COP9 signalosome complex subunit 4, helix turn helix domain / Cop9 signalosome subunit 5 C-terminal domain / CSN4/RPN5/eIF3a helix turn helix domain / Nedd8-like ubiquitin / Eukaryotic translation initiation factor 3 subunit M eIF3m/COP9 signalosome complex subunit 7 COPS7 / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Zinc finger, RING-H2-type / RING-H2 zinc finger domain / : / : / : / PSMD12/CSN4, N-terminal / Cullin protein neddylation domain / 26S proteasome regulatory subunit Rpn7/COP9 signalosome complex subunit 1 / 26S proteasome regulatory subunit Rpn7, N-terminal / 26S proteasome subunit RPN7 / 26S Proteasome non-ATPase regulatory subunit 12/COP9 signalosome complex subunit 4 / : / Cullin, conserved site / Elongin-C / Cullin family signature. / Elongin B / Cullin repeat-like-containing domain superfamily / Cullin protein, neddylation domain / Cullin / Cullin protein neddylation domain / PCI/PINT associated module / Cullin / CSN8/PSMD8/EIF3K / CSN8/PSMD8/EIF3K family / Rpn11/EIF3F, C-terminal / Maintenance of mitochondrial structure and function / Cullin, N-terminal / Cullin homology domain / Cullin homology domain superfamily / Cullin family / Cullin family profile. / : / motif in proteasome subunits, Int-6, Nip-1 and TRIP-15 / PCI domain / Proteasome component (PCI) domain / PCI domain profile. / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / MPN domain / MPN domain profile. / SKP1/BTB/POZ domain superfamily / Zinc finger RING-type profile. / Zinc finger, RING-type / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Tetratricopeptide-like helical domain superfamily / 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 von Hippel-Lindau disease tumor suppressor / COP9 signalosome complex subunit 2 / E3 ubiquitin-protein ligase RBX1 / COP9 signalosome complex subunit 1 / Cullin-2 / Elongin-C / Elongin-B / Ubiquitin-like protein NEDD8 / COP9 signalosome complex subunit 6 / COP9 signalosome complex subunit 5 ... von Hippel-Lindau disease tumor suppressor / COP9 signalosome complex subunit 2 / E3 ubiquitin-protein ligase RBX1 / COP9 signalosome complex subunit 1 / Cullin-2 / Elongin-C / Elongin-B / Ubiquitin-like protein NEDD8 / COP9 signalosome complex subunit 6 / COP9 signalosome complex subunit 5 / COP9 signalosome complex subunit 8 / COP9 signalosome complex subunit 4 / COP9 signalosome complex subunit 7b / COP9 signalosome complex subunit 3 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 : 8.2 Å 詳細 データ登録者Faull SV / Lau AMC 資金援助 英国, 1件 詳細 詳細を隠すOrganization Grant number 国 Cancer Research UK 英国
引用ジャーナル : Nat Commun / 年 : 2019タイトル : Structural basis of Cullin 2 RING E3 ligase regulation by the COP9 signalosome.著者 : Sarah V Faull / Andy M C Lau / Chloe Martens / Zainab Ahdash / Kjetil Hansen / Hugo Yebenes / Carla Schmidt / Fabienne Beuron / Nora B Cronin / Edward P Morris / Argyris Politis / 要旨 : Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. ... Cullin-Ring E3 Ligases (CRLs) regulate a multitude of cellular pathways through specific substrate receptors. The COP9 signalosome (CSN) deactivates CRLs by removing NEDD8 from activated Cullins. Here we present structures of the neddylated and deneddylated CSN-CRL2 complexes by combining single-particle cryo-electron microscopy (cryo-EM) with chemical cross-linking mass spectrometry (XL-MS). These structures suggest a conserved mechanism of CSN activation, consisting of conformational clamping of the CRL2 substrate by CSN2/CSN4, release of the catalytic CSN5/CSN6 heterodimer and finally activation of the CSN5 deneddylation machinery. Using hydrogen-deuterium exchange (HDX)-MS we show that CRL2 activates CSN5/CSN6 in a neddylation-independent manner. The presence of NEDD8 is required to activate the CSN5 active site. Overall, by synergising cryo-EM with MS, we identify sensory regions of the CSN that mediate its stepwise activation and provide a framework for understanding the regulatory mechanism of other Cullin family members. 履歴 登録 2019年3月28日 - ヘッダ(付随情報) 公開 2019年8月28日 - マップ公開 2019年8月28日 - 更新 2024年5月22日 - 現状 2024年5月22日 処理サイト : PDBe / 状態 : 公開
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