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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: EMDB / ID: EMD-22123 | |||||||||||||||
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タイトル | Structure of the human CDK-activating kinase | |||||||||||||||
![]() | Post-processed map, clipped to 150 pixel box size (as used for coordinate refinement) | |||||||||||||||
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機能・相同性 | ![]() cyclin-dependent protein kinase activating kinase holoenzyme complex / ventricular system development / snRNA transcription by RNA polymerase II / CAK-ERCC2 complex / transcription factor TFIIK complex / adult heart development / transcription factor TFIIH core complex / transcription factor TFIIH holo complex / cyclin-dependent protein serine/threonine kinase activator activity / [RNA-polymerase]-subunit kinase ...cyclin-dependent protein kinase activating kinase holoenzyme complex / ventricular system development / snRNA transcription by RNA polymerase II / CAK-ERCC2 complex / transcription factor TFIIK complex / adult heart development / transcription factor TFIIH core complex / transcription factor TFIIH holo complex / cyclin-dependent protein serine/threonine kinase activator activity / [RNA-polymerase]-subunit kinase / RNA Polymerase I Transcription Termination / cyclin-dependent protein serine/threonine kinase regulator activity / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / regulation of G1/S transition of mitotic cell cycle / RNA Polymerase I Transcription Initiation / RNA polymerase II transcribes snRNA genes / Tat-mediated elongation of the HIV-1 transcript / Formation of HIV-1 elongation complex containing HIV-1 Tat / ATP-dependent activity, acting on DNA / cyclin-dependent kinase / Formation of HIV elongation complex in the absence of HIV Tat / cyclin-dependent protein serine/threonine kinase activity / cyclin-dependent protein kinase holoenzyme complex / Cyclin E associated events during G1/S transition / RNA Polymerase II Transcription Elongation / Cyclin A/B1/B2 associated events during G2/M transition / Formation of RNA Pol II elongation complex / Cyclin A:Cdk2-associated events at S phase entry / RNA Polymerase II Pre-transcription Events / RNA polymerase II CTD heptapeptide repeat kinase activity / male germ cell nucleus / nucleotide-excision repair / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / RNA Polymerase I Promoter Escape / positive regulation of smooth muscle cell proliferation / NoRC negatively regulates rRNA expression / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / fibrillar center / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / response to calcium ion / Gap-filling DNA repair synthesis and ligation in TC-NER / G1/S transition of mitotic cell cycle / Cyclin D associated events in G1 / RUNX1 regulates transcription of genes involved in differentiation of HSCs / transcription by RNA polymerase II / protein stabilization / regulation of cell cycle / protein kinase activity / cell division / DNA repair / protein serine kinase activity / protein serine/threonine kinase activity / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / perinuclear region of cytoplasm / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleoplasm / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.8 Å | |||||||||||||||
![]() | Greber BJ / Perez-Bertoldi JM / Lim K / Iavarone AT / Toso DB / Nogales E | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The cryoelectron microscopy structure of the human CDK-activating kinase. 著者: Basil J Greber / Juan M Perez-Bertoldi / Kif Lim / Anthony T Iavarone / Daniel B Toso / Eva Nogales / ![]() 要旨: The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by ...The human CDK-activating kinase (CAK), a complex composed of cyclin-dependent kinase (CDK) 7, cyclin H, and MAT1, is a critical regulator of transcription initiation and the cell cycle. It acts by phosphorylating the C-terminal heptapeptide repeat domain of the RNA polymerase II (Pol II) subunit RPB1, which is an important regulatory event in transcription initiation by Pol II, and it phosphorylates the regulatory T-loop of CDKs that control cell cycle progression. Here, we have determined the three-dimensional (3D) structure of the catalytic module of human CAK, revealing the structural basis of its assembly and providing insight into CDK7 activation in this context. The unique third component of the complex, MAT1, substantially extends the interaction interface between CDK7 and cyclin H, explaining its role as a CAK assembly factor, and it forms interactions with the CDK7 T-loop, which may contribute to enhancing CAK activity. We have also determined the structure of the CAK in complex with the covalently bound inhibitor THZ1 in order to provide insight into the binding of inhibitors at the CDK7 active site and to aid in the rational design of therapeutic compounds. | |||||||||||||||
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 | EMマップ: ![]() ![]() ![]() |
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 12 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 24.4 KB 24.4 KB | 表示 表示 | ![]() |
画像 | ![]() | 141.7 KB | ||
マスクデータ | ![]() | 38.4 MB | ![]() | |
その他 | ![]() ![]() | 29.6 MB 29.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 6xbzMC ![]() 6xd3C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 3.5 TB Data #1: Unaligned movies of human CAK, dataset 1 [micrographs - multiframe] Data #2: Unaligned movies of human CAK, dataset 2 [micrographs - multiframe]) |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Post-processed map, clipped to 150 pixel box size (as used for coordinate refinement) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.22 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
ファイル | ![]() | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Unfiltered half-map (full size)
ファイル | emd_22123_half_map_1.map | ||||||||||||
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注釈 | Unfiltered half-map (full size) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Unfiltered half-map (full size)
ファイル | emd_22123_half_map_2.map | ||||||||||||
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注釈 | Unfiltered half-map (full size) | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Human CDK-activating kinase
全体 | 名称: Human CDK-activating kinase |
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要素 |
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-超分子 #1: Human CDK-activating kinase
超分子 | 名称: Human CDK-activating kinase / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: Recombinantly expressed as a trimeric complex in insect cells |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
分子量 | 理論値: 100 KDa |
-分子 #1: CDK-activating kinase assembly factor MAT1
分子 | 名称: CDK-activating kinase assembly factor MAT1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 38.13234 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MGSSHHHHHH ENLYFQSNAM DDQGCPRCKT TKYRNPSLKL MVNVCGHTLC ESCVDLLFVR GAGNCPECGT PLRKSNFRVQ LFEDPTVDK EVEIRKKVLK IYNKREEDFP SLREYNDFLE EVEEIVFNLT NNVDLDNTKK KMEIYQKENK DVIQKNKLKL T REQEELEE ...文字列: MGSSHHHHHH ENLYFQSNAM DDQGCPRCKT TKYRNPSLKL MVNVCGHTLC ESCVDLLFVR GAGNCPECGT PLRKSNFRVQ LFEDPTVDK EVEIRKKVLK IYNKREEDFP SLREYNDFLE EVEEIVFNLT NNVDLDNTKK KMEIYQKENK DVIQKNKLKL T REQEELEE ALEVERQENE QRRLFIQKEE QLQQILKRKN KQAFLDELES SDLPVALLLA QHKDRSTQLE MQLEKPKPVK PV TFSTGIK MGQHISLAPI HKLEEALYEY QPLQIETYGP HVPELEMLGR LGYLNHVRAA SPQDLAGGYT SSLACHRALQ DAF SGLFWQ PS |
-分子 #2: Cyclin-H
分子 | 名称: Cyclin-H / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 37.695473 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MYHNSSQKRH WTFSSEEQLA RLRADANRKF RCKAVANGKV LPNDPVFLEP HEEMTLCKYY EKRLLEFCSV FKPAMPRSVV GTACMYFKR FYLNNSVMEY HPRIIMLTCA FLACKVDEFN VSSPQFVGNL RESPLGQEKA LEQILEYELL LIQQLNFHLI V HNPYRPFE ...文字列: MYHNSSQKRH WTFSSEEQLA RLRADANRKF RCKAVANGKV LPNDPVFLEP HEEMTLCKYY EKRLLEFCSV FKPAMPRSVV GTACMYFKR FYLNNSVMEY HPRIIMLTCA FLACKVDEFN VSSPQFVGNL RESPLGQEKA LEQILEYELL LIQQLNFHLI V HNPYRPFE GFLIDLKTRY PILENPEILR KTADDFLNRI ALTDAYLLYT PSQIALTAIL SSASRAGITM ESYLSESLML KE NRTCLSQ LLDIMKSMRN LVKKYEPPRS EEVAVLKQKL ERCHSAELAL NVITKKRKGY EDDDYVSKKS KHEEEEWTDD DLV ESL |
-分子 #3: Cyclin-dependent kinase 7
分子 | 名称: Cyclin-dependent kinase 7 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO / EC番号: cyclin-dependent kinase |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 43.731051 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MASWSHPQFE KGGGSGGGSG GGSWSHPQFE KSGGGSENLY FQSNAMALDV KSRAKRYEKL DFLGEGQFAT VYKARDKNTN QIVAIKKIK LGHRSEAKDG INRTALREIK LLQELSHPNI IGLLDAFGHK SNISLVFDFM ETDLEVIIKD NSLVLTPSHI K AYMLMTLQ ...文字列: MASWSHPQFE KGGGSGGGSG GGSWSHPQFE KSGGGSENLY FQSNAMALDV KSRAKRYEKL DFLGEGQFAT VYKARDKNTN QIVAIKKIK LGHRSEAKDG INRTALREIK LLQELSHPNI IGLLDAFGHK SNISLVFDFM ETDLEVIIKD NSLVLTPSHI K AYMLMTLQ GLEYLHQHWI LHRDLKPNNL LLDENGVLKL ADFGLAKSFG (SEP)PNRAYTHQV VTRWYRAPEL LFGARMYG V GVDMWAVGCI LAELLLRVPF LPGDSDLDQL TRIFETLGTP TEEQWPDMCS LPDYVTFKSF PGIPLHHIFS AAGDDLLDL IQGLFLFNPC ARITATQALK MKYFSNRPGP TPGCQLPRPN CPVETLKEQS NPALAIKRKR TEALEQGGLP KKLIF |
-分子 #4: MAGNESIUM ION
分子 | 名称: MAGNESIUM ION / タイプ: ligand / ID: 4 / コピー数: 1 / 式: MG |
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分子量 | 理論値: 24.305 Da |
-分子 #5: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER
分子 | 名称: PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / タイプ: ligand / ID: 5 / コピー数: 1 / 式: AGS |
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分子量 | 理論値: 523.247 Da |
Chemical component information | ![]() ChemComp-AGS: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.2 mg/mL | ||||||||||||||||||
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緩衝液 | pH: 7.9 構成要素:
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グリッド | モデル: UltrAuFoil R1.2/1.3 / 材質: GOLD / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 雰囲気: AIR | ||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 278 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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撮影 | #0 - Image recording ID: 1 #0 - フィルム・検出器のモデル: GATAN K3 (6k x 4k) #0 - 撮影したグリッド数: 1 / #0 - 実像数: 3296 / #0 - 平均露光時間: 2.0 sec. / #0 - 平均電子線量: 69.0 e/Å2 / #0 - 詳細: 69 frames per movie / #1 - Image recording ID: 2 #1 - フィルム・検出器のモデル: GATAN K3 (6k x 4k) #1 - 撮影したグリッド数: 1 / #1 - 実像数: 4286 / #1 - 平均露光時間: 2.0 sec. / #1 - 平均電子線量: 69.0 e/Å2 / #1 - 詳細: 69 frames per movie |
電子線 | 加速電圧: 200 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 50.0 µm / 倍率(補正後): 72886 / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 0.3 µm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Talos Arctica / 画像提供: FEI Company |