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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 6zh2 | ||||||
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タイトル | Cryo-EM structure of DNA-PKcs (State 1) | ||||||
![]() | DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-dependent protein kinase catalytic subunit,DNA-PKcs | ||||||
![]() | DNA BINDING PROTEIN / Kinase / DNA-PKcs / NHEJ / DNA-repair / DNA-PK | ||||||
機能・相同性 | ![]() 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 / regulation of hematopoietic stem cell differentiation / U3 snoRNA binding / T cell lineage commitment / negative regulation of cGAS/STING signaling pathway / maturation of 5.8S rRNA / B cell lineage commitment / double-strand break repair via alternative nonhomologous end joining / 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 / response to gamma radiation / protein-DNA complex / Nonhomologous End-Joining (NHEJ) / small-subunit processome / peptidyl-threonine phosphorylation / protein destabilization / protein modification process / regulation of circadian rhythm / brain development / 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 / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / DNA damage response / chromatin / nucleolus / negative regulation of apoptotic process / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / nucleoplasm / ATP binding / membrane / nucleus / cytosol 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.92 Å | ||||||
![]() | Chaplin, A.K. / Hardwick, S.W. / Chirgadze, D.Y. / Blundell, T.L. | ||||||
資金援助 | ![]()
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![]() | ![]() 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. #1: ![]() タイトル: Dimers of DNA-PK create a stage for DNA-double strand break repair 著者: Chaplin, A.K. / Hardwick, S.W. / Liang, S. / Stavridi, A.K. / Hnizda, A. / Cooper, L.R. / De Oliveira, T.M. / Chirgadze, D.Y. / Blundell, T.L. | ||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 655.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 527.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.7 MB | 表示 | |
XML形式データ | ![]() | 115.4 KB | 表示 | |
CIF形式データ | ![]() | 172.1 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 472056.281 Da / 分子数: 1 / 由来タイプ: 天然 詳細: UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered ...詳細: UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily,UNK residues (X) are unknown elements of the DNA-PKcs molecule that have been numbered arbitrarily 由来: (天然) ![]() 参照: UniProt: P78527, non-specific serine/threonine protein kinase |
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研究の焦点であるリガンドがあるか | N |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: DNA-PKcs (state 1) / タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / 由来: NATURAL |
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分子量 | 値: 0.47 MDa / 実験値: NO |
由来(天然) | 生物種: ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 53.95 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 378084 | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.92 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 38575 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 142.6 Å2 | ||||||||||||||||||||||||
拘束条件 |
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