- EMDB-16936: cGAS-Nucleosome in complex with SPSB3-ELOBC (composite structure) -
+
データを開く
IDまたはキーワード:
読み込み中...
-
基本情報
登録情報
データベース: EMDB / ID: EMD-16936
タイトル
cGAS-Nucleosome in complex with SPSB3-ELOBC (composite structure)
マップデータ
試料
複合体: cGAS-Spsb3-EloBC complex
タンパク質・ペプチド: x 4種
タンパク質・ペプチド: x 6種
DNA: x 2種
リガンド: x 1種
キーワード
cGAS / degradation / UPS / IMMUNE SYSTEM
機能・相同性
機能・相同性情報
2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / target-directed miRNA degradation / elongin complex / regulation of immunoglobulin production / cGAS/STING signaling pathway / VCB complex ...2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / target-directed miRNA degradation / elongin complex / regulation of immunoglobulin production / cGAS/STING signaling pathway / VCB complex / regulation of T cell activation / pattern recognition receptor signaling pathway / Cul5-RING ubiquitin ligase complex / cGMP-mediated signaling / SCF ubiquitin ligase complex / negative regulation of epithelial to mesenchymal transition / Cul2-RING ubiquitin ligase complex / STAT family protein binding / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cellular response to exogenous dsRNA / RSV-host interactions / ubiquitin-like protein ligase binding / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / positive regulation of type I interferon production / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / negative regulation of double-strand break repair via homologous recombination / ubiquitin-like ligase-substrate adaptor activity / cAMP-mediated signaling / Formation of HIV elongation complex in the absence of HIV Tat / negative regulation of megakaryocyte differentiation / protein K48-linked ubiquitination / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / nucleosome binding / Replacement of protamines by nucleosomes in the male pronucleus / RNA Polymerase II Transcription Elongation / CENP-A containing nucleosome / Formation of RNA Pol II elongation complex / Packaging Of Telomere Ends / positive regulation of defense response to virus by host / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / phosphatidylinositol-4,5-bisphosphate binding / RNA Polymerase II Pre-transcription Events / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / telomere organization / Interleukin-7 signaling / Inhibition of DNA recombination at telomere / RNA Polymerase I Promoter Opening / Meiotic synapsis / activation of innate immune response / Assembly of the ORC complex at the origin of replication / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / transcription corepressor binding / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Vif-mediated degradation of APOBEC3G / determination of adult lifespan / HDMs demethylate histones / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / Inactivation of CSF3 (G-CSF) signaling / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / transcription elongation by RNA polymerase II / Evasion by RSV of host interferon responses / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Transcriptional regulation by small RNAs / molecular condensate scaffold activity / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Regulation of expression of SLITs and ROBOs / G2/M DNA damage checkpoint / Metalloprotease DUBs / NoRC negatively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis 類似検索 - 分子機能
ジャーナル: Nature / 年: 2024 タイトル: The CRL5-SPSB3 ubiquitin ligase targets nuclear cGAS for degradation. 著者: Pengbiao Xu / Ying Liu / Chong Liu / Baptiste Guey / Lingyun Li / Pauline Melenec / Jonathan Ricci / Andrea Ablasser / 要旨: Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2'3'-cyclic GMP-AMP (cGAMP). ...Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2'3'-cyclic GMP-AMP (cGAMP). The indiscriminate activity of cGAS towards DNA demands tight regulatory mechanisms that are necessary to maintain cell and tissue homeostasis under normal conditions. Inside the cell nucleus, anchoring to nucleosomes and competition with chromatin architectural proteins jointly prohibit cGAS activation by genomic DNA. However, the fate of nuclear cGAS and its role in cell physiology remains unclear. Here we show that the ubiquitin proteasomal system (UPS) degrades nuclear cGAS in cycling cells. We identify SPSB3 as the cGAS-targeting substrate receptor that associates with the cullin-RING ubiquitin ligase 5 (CRL5) complex to ligate ubiquitin onto nuclear cGAS. A cryo-electron microscopy structure of nucleosome-bound cGAS in a complex with SPSB3 reveals a highly conserved Asn-Asn (NN) minimal degron motif at the C terminus of cGAS that directs SPSB3 recruitment, ubiquitylation and cGAS protein stability. Interference with SPSB3-regulated nuclear cGAS degradation primes cells for type I interferon signalling, conferring heightened protection against infection by DNA viruses. Our research defines protein degradation as a determinant of cGAS regulation in the nucleus and provides structural insights into an element of cGAS that is amenable to therapeutic exploitation.