- EMDB-11217: Cryo-EM structure of DNA-PK monomer -
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基本情報
登録情報
データベース: EMDB / ID: EMD-11217
タイトル
Cryo-EM structure of DNA-PK monomer
マップデータ
試料
複合体: DNA-PK monomer
複合体: DNA-dependent protein kinase catalytic subunit
タンパク質・ペプチド: DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-PKcs
複合体: X-ray repair cross-complementing protein 5+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
複合体: DNA
DNA: DNA
DNA: DNA
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
positive regulation of platelet formation / Ku70:Ku80 complex / negative regulation of t-circle formation / T cell receptor V(D)J recombination / DNA end binding / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase complex / DNA-dependent protein kinase-DNA ligase 4 complex ...positive regulation of platelet formation / Ku70:Ku80 complex / negative regulation of t-circle formation / T cell receptor V(D)J recombination / DNA end binding / pro-B cell differentiation / small-subunit processome assembly / positive regulation of lymphocyte differentiation / DNA-dependent protein kinase complex / DNA-dependent protein kinase-DNA ligase 4 complex / nonhomologous end joining complex / immunoglobulin V(D)J recombination / immature B cell differentiation / regulation of smooth muscle cell proliferation / cellular response to X-ray / nuclear telomere cap complex / double-strand break repair via alternative nonhomologous end joining / double-strand break repair via classical nonhomologous end joining / regulation of epithelial cell proliferation / telomere capping / Cytosolic sensors of pathogen-associated DNA / IRF3-mediated induction of type I IFN / positive regulation of neurogenesis / regulation of hematopoietic stem cell differentiation / regulation of telomere maintenance / cellular response to fatty acid / recombinational repair / U3 snoRNA binding / cellular hyperosmotic salinity response / protein localization to chromosome, telomeric region / T cell lineage commitment / maturation of 5.8S rRNA / negative regulation of cGAS/STING signaling pathway / positive regulation of double-strand break repair via nonhomologous end joining / B cell lineage commitment / telomeric DNA binding / 2-LTR circle formation / hematopoietic stem cell proliferation / negative regulation of protein phosphorylation / positive regulation of protein kinase activity / 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 / ATP-dependent activity, acting on DNA / ectopic germ cell programmed cell death / telomere maintenance via telomerase / somitogenesis / peptidyl-threonine phosphorylation / neurogenesis / mitotic G1 DNA damage checkpoint signaling / DNA helicase activity / telomere maintenance / activation of innate immune response / cyclin binding / positive regulation of erythrocyte differentiation / cellular response to leukemia inhibitory factor / positive regulation of translation / response to gamma radiation / Nonhomologous End-Joining (NHEJ) / small-subunit processome / enzyme activator activity / cellular response to gamma radiation / regulation of circadian rhythm / protein-DNA complex / protein destabilization / brain development / protein modification process / 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 / double-strand break repair via nonhomologous end joining / cellular response to insulin stimulus / intrinsic apoptotic signaling pathway in response to DNA damage / rhythmic process / peptidyl-serine phosphorylation / E3 ubiquitin ligases ubiquitinate target proteins / double-strand break repair / DNA-dependent protein kinase activity / histone H2AXS139 kinase activity / T cell differentiation in thymus / heart development / double-stranded DNA binding / scaffold protein binding / secretory granule lumen / DNA recombination / transcription regulator complex / RNA polymerase II-specific DNA-binding transcription factor binding / ficolin-1-rich granule lumen / damaged DNA binding / chromosome, telomeric region / non-specific serine/threonine protein kinase / transcription cis-regulatory region binding / protein kinase activity / protein phosphorylation / positive regulation of apoptotic process / response to xenobiotic stimulus / protein domain specific binding / ribonucleoprotein complex / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity 類似検索 - 分子機能
Ku70, bridge and pillars domain superfamily / : / Ku70 / 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 ...Ku70, bridge and pillars domain superfamily / : / Ku70 / 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 / Ku, C-terminal / Ku, C-terminal domain superfamily / Ku C terminal domain like / Ku80 / Ku70/Ku80 C-terminal arm / Ku70/Ku80 C-terminal arm / Ku70/Ku80, N-terminal alpha/beta / Ku70/Ku80 beta-barrel domain / 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 / SPOC-like, C-terminal domain superfamily / SAP domain superfamily / SAP motif profile. / SAP domain / Putative DNA-binding (bihelical) motif predicted to be involved in chromosomal organisation / SAP domain / : / FATC domain / PIK-related kinase, FAT / FAT 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
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.
複合体: DNA-dependent protein kinase catalytic subunit
タンパク質・ペプチド: DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-PKcs
複合体: X-ray repair cross-complementing protein 5+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