登録情報 データベース : EMDB / ID : EMD-19047 ダウンロードとリンクタイトル Structure of Integrator-PP2A complex マップデータOverall map filtered by local resolution 詳細 試料複合体 : Integrator-PP2A complex複合体 : Integrator-PP2A complex複合体 : DSS1リガンド : x 2種 詳細 キーワード Integrator complex / Post-termination complex / RNA Polymerase II / Pol II / RNAPII / TRANSCRIPTION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
U2 snRNA 3'-end processing / regulation of fertilization / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / snRNA 3'-end processing / protein serine/threonine phosphatase complex / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression ... U2 snRNA 3'-end processing / regulation of fertilization / meiotic spindle elongation / Integration of energy metabolism / PP2A-mediated dephosphorylation of key metabolic factors / regulation of microtubule binding / snRNA 3'-end processing / protein serine/threonine phosphatase complex / mitotic sister chromatid separation / MASTL Facilitates Mitotic Progression / regulation of meiotic cell cycle process involved in oocyte maturation / protein phosphatase type 2A complex / meiotic sister chromatid cohesion, centromeric / snRNA processing / peptidyl-serine dephosphorylation / flagellated sperm motility / peptidyl-threonine dephosphorylation / FAR/SIN/STRIPAK complex / protein localization to nuclear envelope / positive regulation of microtubule binding / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / Inhibition of replication initiation of damaged DNA by RB1/E2F1 / female meiotic nuclear division / protein phosphatase regulator activity / protein antigen binding / GABA receptor binding / integrator complex / regulation of transcription elongation by RNA polymerase II / APC truncation mutants have impaired AXIN binding / AXIN missense mutants destabilize the destruction complex / Truncations of AMER1 destabilize the destruction complex / Initiation of Nuclear Envelope (NE) Reformation / ERKs are inactivated / positive regulation of extrinsic apoptotic signaling pathway in absence of ligand / Beta-catenin phosphorylation cascade / Signaling by GSK3beta mutants / CTNNB1 S33 mutants aren't phosphorylated / CTNNB1 S37 mutants aren't phosphorylated / CTNNB1 S45 mutants aren't phosphorylated / CTNNB1 T41 mutants aren't phosphorylated / 加水分解酵素; エステル加水分解酵素; 3'-リン酸モノエステル産生エンドリボヌクレアーゼ / negative regulation of epithelial to mesenchymal transition / regulation of growth / Disassembly of the destruction complex and recruitment of AXIN to the membrane / centrosome localization / inner cell mass cell proliferation / negative regulation of glycolytic process through fructose-6-phosphate / positive regulation of NLRP3 inflammasome complex assembly / myosin phosphatase activity / CTLA4 inhibitory signaling / protein serine/threonine phosphatase activity / Platelet sensitization by LDL / protein-serine/threonine phosphatase / Cyclin A/B1/B2 associated events during G2/M transition / regulation of cell differentiation / negative regulation of hippo signaling / ERK/MAPK targets / T cell homeostasis / regulation of mitotic cell cycle / regulation of G1/S transition of mitotic cell cycle / mesoderm development / phosphoprotein phosphatase activity / RNA polymerase II transcribes snRNA genes / chromosome, centromeric region / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / DARPP-32 events / lateral plasma membrane / meiotic cell cycle / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / Recruitment of NuMA to mitotic centrosomes / Anchoring of the basal body to the plasma membrane / Resolution of Sister Chromatid Cohesion / RNA endonuclease activity / embryo implantation / protein dephosphorylation / AURKA Activation by TPX2 / mitotic spindle organization / negative regulation of transforming growth factor beta receptor signaling pathway / DNA damage checkpoint signaling / protein tyrosine phosphatase activity / chromosome segregation / RHO GTPases Activate Formins / cellular response to ionizing radiation / response to lead ion / RAF activation / regulation of protein phosphorylation / Spry regulation of FGF signaling / Degradation of beta-catenin by the destruction complex / tau protein binding / positive regulation of protein serine/threonine kinase activity / PKR-mediated signaling / Cyclin D associated events in G1 / transmembrane signaling receptor activity / spindle pole 類似検索 - 分子機能 Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / Integrator complex subunit 1, RP2B-binding domain / Integrator complex subunit 2 / : / INTS6/SAGE1/DDX26B/CT45, C-terminal / INTS6/SAGE1/DDX26B/CT45 C-terminus ... Domain of unknown function DUF3677 / Integrator complex subunit 2, metazoa / Integrator complex subunit 2 / Integrator complex subunit 7 / Integrator complex subunit 1 / Integrator complex subunit 1, RP2B-binding domain / Integrator complex subunit 2 / : / INTS6/SAGE1/DDX26B/CT45, C-terminal / INTS6/SAGE1/DDX26B/CT45 C-terminus / Integrator complex subunit 10 / Integrator complex subunit 15 / Integrator complex subunit 5, C-terminal / Integrator complex subunit 5, N-terminal / Integrator complex subunit 8 / Integrator complex subunit 14 / Integrator complex subunit 5 / Integrator complex subunit 14, beta-barrel domain / Integrator complex subunit 14, C-terminal / Integrator complex subunit 5 N-terminus / Integrator complex subunit 5 C-terminus / Integrator complex subunit 15 / Integrator complex subunit 14, beta-barrel domain / Integrator complex subunit 14, alpha-helical domain / Integrator subunit 10 / Cell cycle regulator Mat89Bb / Cell cycle and development regulator Mat89Bb / Sister chromatid cohesion protein PDS5 protein / : / Integrator IntS9, C-terminal domain / Integrator complex subunit 9 / Integrator complex subunit 11, MBL-fold / : / Integrator IntS11, C-terminal domain / : / : / : / Metallo-beta-lactamase superfamily domain / Beta-Casp domain / Beta-Casp domain / Beta-Casp domain / Zn-dependent metallo-hydrolase, RNA specificity domain / Zn-dependent metallo-hydrolase RNA specificity domain / HEAT repeat / HEAT repeat / Serine/threonine specific protein phosphatases signature. / Protein phosphatase 2A homologues, catalytic domain. / Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase / HEAT repeat profile. / HEAT, type 2 / von Willebrand factor type A domain / HEAT repeats / Calcineurin-like phosphoesterase domain, ApaH type / Calcineurin-like phosphoesterase / Metallo-dependent phosphatase-like / VWFA domain profile. / Metallo-beta-lactamase superfamily / von Willebrand factor, type A / Metallo-beta-lactamase / von Willebrand factor A-like domain superfamily / Ribonuclease Z/Hydroxyacylglutathione hydrolase-like / Armadillo-like helical / Tetratricopeptide-like helical domain superfamily / Armadillo-type fold 類似検索 - ドメイン・相同性 Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / Integrator complex subunit 11 / Integrator complex subunit 5 / Integrator complex subunit 8 / Integrator complex subunit 1 / Integrator complex subunit 4 / Integrator complex subunit 15 / Integrator complex subunit 14 / Integrator complex subunit 2 ... Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform / Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform / Integrator complex subunit 11 / Integrator complex subunit 5 / Integrator complex subunit 8 / Integrator complex subunit 1 / Integrator complex subunit 4 / Integrator complex subunit 15 / Integrator complex subunit 14 / Integrator complex subunit 2 / Integrator complex subunit 9 / Integrator complex subunit 7 / Integrator complex subunit 13 / Integrator complex subunit 10 / Integrator complex subunit 6 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Trichoplusia ni (イラクサキンウワバ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.1 Å 詳細 データ登録者Fianu I / Ochmann M / Walshe JL / Cramer P 資金援助 ドイツ, European Union, 3件 詳細 詳細を隠すOrganization Grant number 国 German Research Foundation (DFG) SFB860 ドイツ German Research Foundation (DFG) SFB1565 ドイツ European Research Council (ERC) EXC 2067/1-390729940 European Union
引用ジャーナル : Nature / 年 : 2024タイトル : Structural basis of Integrator-dependent RNA polymerase II termination.著者 : Isaac Fianu / Moritz Ochmann / James L Walshe / Olexandr Dybkov / Joseph Neos Cruz / Henning Urlaub / Patrick Cramer / 要旨 : The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex ... The Integrator complex can terminate RNA polymerase II (Pol II) in the promoter-proximal region of genes. Previous work has shed light on how Integrator binds to the paused elongation complex consisting of Pol II, the DRB sensitivity-inducing factor (DSIF) and the negative elongation factor (NELF) and how it cleaves the nascent RNA transcript, but has not explained how Integrator removes Pol II from the DNA template. Here we present three cryo-electron microscopy structures of the complete Integrator-PP2A complex in different functional states. The structure of the pre-termination complex reveals a previously unresolved, scorpion-tail-shaped INTS10-INTS13-INTS14-INTS15 module that may use its 'sting' to open the DSIF DNA clamp and facilitate termination. The structure of the post-termination complex shows that the previously unresolved subunit INTS3 and associated sensor of single-stranded DNA complex (SOSS) factors prevent Pol II rebinding to Integrator after termination. The structure of the free Integrator-PP2A complex in an inactive closed conformation reveals that INTS6 blocks the PP2A phosphatase active site. These results lead to a model for how Integrator terminates Pol II transcription in three steps that involve major rearrangements. 履歴 登録 2023年12月6日 - ヘッダ(付随情報) 公開 2024年2月7日 - マップ公開 2024年2月7日 - 更新 2024年5月15日 - 現状 2024年5月15日 処理サイト : PDBe / 状態 : 公開
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