登録情報 データベース : EMDB / ID : EMD-11219 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of DNA-PK dimer マップデータ 詳細 試料細胞器官・細胞要素 : DNA-PK dimer細胞器官・細胞要素 : DNA-dependent protein kinase catalytic subunitタンパク質・ペプチド : DNA-dependent protein kinase catalytic subunit,DNA-PKcs細胞器官・細胞要素 : X-ray repair cross-complementing proteins 5 and 6タンパク質・ペプチド : X-ray repair cross-complementing protein 6タンパク質・ペプチド : X-ray repair cross-complementing protein 5細胞器官・細胞要素 : DNADNA : DNA (25-MER)DNA : DNA (27-MER)DNA : DNA (26-MER)DNA : DNA (28-MER) 詳細 キーワード Kinase / DNA-PKcs / NHEJ / DNA-repair / DNA-PK / DNA BINDING PROTEIN / Ku70/80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
Ku70:Ku80 complex / negative regulation of t-circle formation / positive regulation of platelet formation / DNA end binding / 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 ... Ku70:Ku80 complex / negative regulation of t-circle formation / positive regulation of platelet formation / DNA end binding / 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 / cellular response to X-ray / immunoglobulin V(D)J recombination / nonhomologous end joining complex / DNA ligation / regulation of smooth muscle cell proliferation / nuclear telomere cap complex / Cytosolic sensors of pathogen-associated DNA / double-strand break repair via classical nonhomologous end joining / regulation of epithelial cell proliferation / IRF3-mediated induction of type I IFN / telomere capping / recombinational repair / regulation of telomere maintenance / regulation of hematopoietic stem cell differentiation / U3 snoRNA binding / positive regulation of neurogenesis / cellular response to fatty acid / hematopoietic stem cell proliferation / protein localization to chromosome, telomeric region / cellular hyperosmotic salinity response / T cell lineage commitment / negative regulation of cGAS/STING signaling pathway / telomeric DNA binding / maturation of 5.8S rRNA / positive regulation of catalytic activity / B cell lineage commitment / double-strand break repair via alternative nonhomologous end joining / 2-LTR circle formation / positive regulation of double-strand break repair via nonhomologous end joining / site of DNA damage / 付加脱離酵素(リアーゼ); 炭素-酸素リアーゼ類; その他の炭素-酸素リアーゼ / 5'-deoxyribose-5-phosphate lyase activity / hematopoietic stem cell differentiation / positive regulation of protein kinase activity / ectopic germ cell programmed cell death / ATP-dependent activity, acting on DNA / somitogenesis / DNA helicase activity / positive regulation of telomerase activity / enzyme activator activity / mitotic G1 DNA damage checkpoint signaling / positive regulation of telomere maintenance via telomerase / activation of innate immune response / telomere maintenance / cyclin binding / neurogenesis / positive regulation of erythrocyte differentiation / negative regulation of protein phosphorylation / cellular response to leukemia inhibitory factor / positive regulation of translation / response to gamma radiation / protein-DNA complex / Nonhomologous End-Joining (NHEJ) / small-subunit processome / peptidyl-threonine phosphorylation / 加水分解酵素; 酸無水物に作用; 酸無水物に作用・細胞または細胞小器官の運動に関与 / protein destabilization / protein modification process / regulation of circadian rhythm / brain development / cellular response to gamma radiation / 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 / scaffold protein binding / double-stranded DNA binding / peptidyl-serine phosphorylation / DNA recombination / secretory granule lumen / RNA polymerase II-specific DNA-binding transcription factor binding / ficolin-1-rich granule lumen / transcription regulator complex / chromosome, telomeric region / damaged DNA binding / non-specific serine/threonine protein kinase / transcription cis-regulatory region binding / protein kinase activity / ribonucleoprotein complex / response to xenobiotic stimulus / positive regulation of apoptotic process / protein domain specific binding / protein phosphorylation 類似検索 - 分子機能 Ku70, bridge and pillars domain superfamily / : / Ku70 / Ku, C-terminal / Ku, C-terminal domain superfamily / Ku C terminal domain like / Ku80 / Ku70/Ku80 C-terminal arm / Ku70/Ku80, N-terminal alpha/beta / Ku70/Ku80 beta-barrel domain ... Ku70, bridge and pillars domain superfamily / : / Ku70 / Ku, C-terminal / Ku, C-terminal domain superfamily / Ku C terminal domain like / Ku80 / Ku70/Ku80 C-terminal arm / Ku70/Ku80, N-terminal alpha/beta / Ku70/Ku80 beta-barrel domain / Ku70/Ku80 C-terminal arm / Ku70/Ku80 N-terminal alpha/beta domain / Ku70 and Ku80 are 70kDa and 80kDa subunits of the Lupus Ku autoantigen / Ku70/Ku80 beta-barrel domain / DNA-dependent protein kinase catalytic subunit, CC3 / SPOC-like, C-terminal domain superfamily / 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 / SAP domain superfamily / SAP domain / SAP motif profile. / Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation / SAP domain / 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 / von Willebrand factor (vWF) type A domain / von Willebrand factor, type A / von Willebrand factor A-like domain superfamily / Armadillo-like helical / Armadillo-type fold / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性 X-ray repair cross-complementing protein 6 / X-ray repair cross-complementing protein 5 / DNA-dependent protein kinase catalytic subunit 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 : 7.24 Å 詳細 データ登録者Chaplin AK / Hardwick SW 資金援助 英国, 1件 詳細 詳細を隠すOrganization Grant number 国 Wellcome Trust 200814/Z/16/Z 英国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2021タイトル : Dimers of DNA-PK create a stage for DNA double-strand break repair.
著者 :
Amanda K Chaplin / Steven W Hardwick / Shikang Liang / Antonia Kefala Stavridi / Ales Hnizda / Lee R Cooper / Taiana Maia De Oliveira / Dimitri Y Chirgadze / Tom L Blundell / 要旨 :
DNA double-strand breaks are the most dangerous type of DNA damage and, if not repaired correctly, can lead to cancer. In humans, Ku70/80 recognizes DNA broken ends and recruits the DNA-dependent ... DNA double-strand breaks are the most dangerous type of DNA damage and, if not repaired correctly, can lead to cancer. In humans, Ku70/80 recognizes DNA broken ends and recruits the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form DNA-dependent protein kinase holoenzyme (DNA-PK) in the process of non-homologous end joining (NHEJ). We present a 2.8-Å-resolution cryo-EM structure of DNA-PKcs, allowing precise amino acid sequence registration in regions uninterpreted in previous 4.3-Å X-ray maps. We also report a cryo-EM structure of DNA-PK at 3.5-Å resolution and reveal a dimer mediated by the Ku80 C terminus. Central to dimer formation is a domain swap of the conserved C-terminal helix of Ku80. Our results suggest a new mechanism for NHEJ utilizing a DNA-PK dimer to bring broken DNA ends together. Furthermore, drug inhibition of NHEJ in combination with chemo- and radiotherapy has proved successful, making these models central to structure-based drug targeting efforts. 残り1件を表示 表示を減らす履歴 登録 2020年6月23日 - ヘッダ(付随情報) 公開 2020年10月21日 - マップ公開 2020年10月21日 - 更新 2024年5月1日 - 現状 2024年5月1日 処理サイト : PDBe / 状態 : 公開
すべて表示 表示を減らす