- EMDB-4742: Structural basis of Cullin-2 RING E3 ligase regulation by the COP... -
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基本情報
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データベース: EMDB / ID: EMD-4742
タイトル
Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome
マップデータ
Structural basis of Cullin-2 RING E3 ligase regulation by the COP9 signalosome
試料
複合体: CSN-CRL2-N8
タンパク質・ペプチド: x 13種
リガンド: x 2種
機能・相同性
機能・相同性情報
nucleotide-excision repair factor 4 complex / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / global genome nucleotide-excision repair / exosomal secretion / deNEDDylase activity / GTPase inhibitor activity ...nucleotide-excision repair factor 4 complex / regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / COP9 signalosome assembly / trophectodermal cell proliferation / macrophage migration inhibitory factor binding / regulation of IRE1-mediated unfolded protein response / global genome nucleotide-excision repair / exosomal secretion / deNEDDylase activity / GTPase inhibitor activity / regulation of protein neddylation / protein deneddylation / eukaryotic translation initiation factor 3 complex / activation of NF-kappaB-inducing kinase activity / cullin-RING-type E3 NEDD8 transferase / cellular response to chemical stress / NEDD8 transferase activity / cullin-RING ubiquitin ligase complex / COP9 signalosome / 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 / regulation of proteolysis / target-directed miRNA degradation / elongin complex / VCB complex / positive regulation of protein autoubiquitination / protein neddylation / regulation of JNK cascade / metal-dependent deubiquitinase activity / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / NEDD8 ligase activity / Cul5-RING ubiquitin ligase complex / negative regulation of response to oxidative stress / RHOBTB1 GTPase cycle / ubiquitin-ubiquitin ligase activity / Cul4A-RING E3 ubiquitin ligase complex / SCF ubiquitin ligase complex / inner cell mass cell proliferation / Cul2-RING ubiquitin ligase complex / 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 / TP53 Regulates Transcription of DNA Repair Genes / Prolactin receptor signaling / skeletal muscle cell differentiation / protein monoubiquitination / TGF-beta receptor signaling activates SMADs / cullin family protein binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / Antigen processing: Ubiquitination & Proteasome degradation / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / response to light stimulus / anatomical structure morphogenesis / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / protein K48-linked ubiquitination / Formation of HIV elongation complex in the absence of HIV Tat / post-translational protein modification / Nuclear events stimulated by ALK signaling in cancer / regulation of cellular response to insulin stimulus / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / response to UV / JNK cascade / RNA Polymerase II Pre-transcription Events / positive regulation of TORC1 signaling / T cell activation / translation initiation factor activity / Regulation of BACH1 activity / intrinsic apoptotic signaling pathway / cellular response to amino acid stimulus / transcription corepressor binding / Degradation of DVL / nucleotide-excision repair / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / Recognition of DNA damage by PCNA-containing replication complex / Degradation of GLI1 by the proteasome / transcription elongation by RNA polymerase II / 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 / positive regulation of DNA-binding transcription factor activity / 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 / protein modification process / RING-type E3 ubiquitin transferase / negative regulation of canonical Wnt signaling pathway / Degradation of beta-catenin by the destruction complex / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha 類似検索 - 分子機能
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.