登録情報 データベース : EMDB / ID : EMD-22623 構造の表示 ダウンロードとリンクタイトル CryoEM structure of DNA-PK catalytic subunit complexed with DNA (Complex II) マップデータ 詳細 試料複合体 : complex IIタンパク質・ペプチド : DNA-dependent protein kinase catalytic subunitDNA : DNA (5'-D(P*GP*CP*AP*TP*GP*CP*TP*CP*TP*AP*CP*TP*GP*CP*TP*TP*CP*GP*AP*TP*AP*TP*CP*G)-3')DNA : DNA (5'-D(P*AP*AP*GP*CP*AP*GP*TP*AP*GP*AP*GP*CP*AP*TP*GP*C)-3') 詳細 キーワード NHEJ (非相同末端結合) / V(D)J recombination (V(D)J遺伝子再構成) / DNA repair (DNA修復) / DNA BINDING PROTEIN (DNA結合タンパク質) / DNA BINDING PROTEIN-DNA complex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
positive regulation of platelet formation / T cell receptor V(D)J recombination / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / DNA-dependent protein kinase complex / immature B cell differentiation / DNA-dependent protein kinase-DNA ligase 4 complex ... positive regulation of platelet formation / T cell receptor V(D)J recombination / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / DNA-dependent protein kinase complex / immature B cell differentiation / DNA-dependent protein kinase-DNA ligase 4 complex / immunoglobulin V(D)J recombination / nonhomologous end joining complex / regulation of smooth muscle cell proliferation / Cytosolic sensors of pathogen-associated DNA / regulation of epithelial cell proliferation / IRF3-mediated induction of type I IFN / telomere capping / double-strand break repair via alternative nonhomologous end joining / regulation of hematopoietic stem cell differentiation / U3 snoRNA binding / maturation of 5.8S rRNA / T cell lineage commitment / negative regulation of cGAS/STING signaling pathway / B cell lineage commitment / positive regulation of double-strand break repair via nonhomologous end joining / ectopic germ cell programmed cell death / somitogenesis / mitotic G1 DNA damage checkpoint signaling / activation of innate immune response / telomere maintenance / positive regulation of erythrocyte differentiation / negative regulation of protein phosphorylation / positive regulation of translation / small-subunit processome / デオキシリボ核酸 / response to gamma radiation / Nonhomologous End-Joining (NHEJ) / peptidyl-threonine phosphorylation / protein destabilization / brain development / protein modification process / regulation of circadian rhythm / double-strand break repair via nonhomologous end joining / cellular response to insulin stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / double-strand break repair / rhythmic process / E3 ubiquitin ligases ubiquitinate target proteins / heart development / T cell differentiation in thymus / double-stranded DNA binding / peptidyl-serine phosphorylation / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / chromosome, telomeric region / non-specific serine/threonine protein kinase / protein kinase activity / positive regulation of apoptotic process / protein domain specific binding / protein phosphorylation / protein serine kinase activity / 自然免疫系 / protein serine/threonine kinase activity / DNA damage response / クロマチン / 核小体 / negative regulation of apoptotic process / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / 核質 / ATP binding / 生体膜 / 細胞核 / 細胞質基質 類似検索 - 分子機能 DNA-dependent protein kinase catalytic subunit, CC3 / DNA-dependent protein kinase catalytic subunit, catalytic domain / DNA-dependent protein kinase catalytic subunit, CC5 / DNA-dependent protein kinase catalytic subunit, CC1/2 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC3 / DNA-PKcs, CC5 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC1/2 / NUC194 ... DNA-dependent protein kinase catalytic subunit, CC3 / DNA-dependent protein kinase catalytic subunit, catalytic domain / DNA-dependent protein kinase catalytic subunit, CC5 / DNA-dependent protein kinase catalytic subunit, CC1/2 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC3 / DNA-PKcs, CC5 / DNA-PKcs, N-terminal / DNA-dependent protein kinase catalytic subunit, CC1/2 / NUC194 / PIK-related kinase, FAT / FAT domain / FATC domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC domain profile. / Phosphatidylinositol 3- and 4-kinases signature 1. / Phosphatidylinositol 3/4-kinase, conserved site / Phosphatidylinositol 3- and 4-kinases signature 2. / Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic domain / Armadillo-like helical / Armadillo-type fold / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 DNA-dependent protein kinase catalytic subunit 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / synthetic construct (人工物) 手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 4.3 Å 詳細 データ登録者Chen X / Gellert M 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK) 米国
引用ジャーナル : Mol Cell / 年 : 2021タイトル : Structure of an activated DNA-PK and its implications for NHEJ.著者 : Xuemin Chen / Xiang Xu / Yun Chen / Joyce C Cheung / Huaibin Wang / Jiansen Jiang / Natalia de Val / Tara Fox / Martin Gellert / Wei Yang / 要旨 : DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of ... DNA-dependent protein kinase (DNA-PK), like all phosphatidylinositol 3-kinase-related kinases (PIKKs), is composed of conserved FAT and kinase domains (FATKINs) along with solenoid structures made of HEAT repeats. These kinases are activated in response to cellular stress signals, but the mechanisms governing activation and regulation remain unresolved. For DNA-PK, all existing structures represent inactive states with resolution limited to 4.3 Å at best. Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms at resolutions of 3.7 Å overall and 3.2 Å for FATKINs. These structures reveal the sequential transition of DNA-PK from inactive to activated forms. Most notably, activation of the kinase involves previously unknown stretching and twisting within individual solenoid segments and loosens DNA-end binding. This unprecedented structural plasticity of helical repeats may be a general regulatory mechanism of HEAT-repeat proteins. 履歴 登録 2020年9月7日 - ヘッダ(付随情報) 公開 2021年1月6日 - マップ公開 2021年1月6日 - 更新 2024年3月6日 - 現状 2024年3月6日 処理サイト : RCSB / 状態 : 公開
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