+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 5xzc | ||||||
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タイトル | Cryo-EM structure of p300-p53 protein complex | ||||||
要素 |
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キーワード | TRANSCRIPTION (転写 (生物学)) / transcription factor (転写因子) / autoacetylation / allosteric interaction / catalytically active form | ||||||
機能・相同性 | 機能・相同性情報 behavioral defense response / protein propionyltransferase activity / peptidyl-lysine propionylation / histone lactyltransferase activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / 水泳 / peptide butyryltransferase activity ...behavioral defense response / protein propionyltransferase activity / peptidyl-lysine propionylation / histone lactyltransferase activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / histone H3K122 acetyltransferase activity / 水泳 / peptide butyryltransferase activity / histone H2B acetyltransferase activity / 走性 / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / NOTCH2 intracellular domain regulates transcription / lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / peptidyl-lysine acetylation / histone H3 acetyltransferase activity / histone H4 acetyltransferase activity / cellular response to L-leucine / internal peptidyl-lysine acetylation / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / acetylation-dependent protein binding / STAT3 nuclear events downstream of ALK signaling / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / NGF-stimulated transcription / histone H3K27 acetyltransferase activity / histone H3K18 acetyltransferase activity / Polo-like kinase mediated events / N-terminal peptidyl-lysine acetylation / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / regulation of androgen receptor signaling pathway / NFE2L2 regulating MDR associated enzymes / positive regulation by host of viral transcription / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / : / : / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / Activation of NOXA and translocation to mitochondria / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / negative regulation of helicase activity / regulation of cell cycle G2/M phase transition / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / regulation of mitochondrion organization / oxidative stress-induced premature senescence / oligodendrocyte apoptotic process / negative regulation of miRNA processing / positive regulation of thymocyte apoptotic process / glucose catabolic process to lactate via pyruvate / regulation of tissue remodeling / face morphogenesis / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / 転写 (生物学) / bone marrow development / RUNX3 regulates NOTCH signaling / circadian behavior / histone deacetylase regulator activity / T cell proliferation involved in immune response / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of FOXO transcriptional activity by acetylation / germ cell nucleus / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / regulation of DNA damage response, signal transduction by p53 class mediator / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / Regulation of NFE2L2 gene expression / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / NOTCH3 Intracellular Domain Regulates Transcription / regulation of glycolytic process / TRAF6 mediated IRF7 activation / negative regulation of neuroblast proliferation / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / platelet formation / megakaryocyte development / peptide-lysine-N-acetyltransferase activity / nuclear androgen receptor binding / NFE2L2 regulating anti-oxidant/detoxification enzymes / regulation of tubulin deacetylation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / macrophage derived foam cell differentiation / negative regulation of glial cell proliferation / Regulation of TP53 Activity through Association with Co-factors / FOXO-mediated transcription of cell death genes / NFE2L2 regulating tumorigenic genes 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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: 10.7 Å | ||||||
データ登録者 | Ghosh, R. / Roy, S. / Sengupta, J. | ||||||
引用 | ジャーナル: Biochemistry / 年: 2019 タイトル: Tumor Suppressor p53-Mediated Structural Reorganization of the Transcriptional Coactivator p300. 著者: Raka Ghosh / Stephanie Kaypee / Manidip Shasmal / Tapas K Kundu / Siddhartha Roy / Jayati Sengupta / 要旨: Transcriptional coactivator p300, a critical player in eukaryotic gene regulation, primarily functions as a histone acetyltransferase (HAT). It is also an important player in acetylation of a number ...Transcriptional coactivator p300, a critical player in eukaryotic gene regulation, primarily functions as a histone acetyltransferase (HAT). It is also an important player in acetylation of a number of nonhistone proteins, p53 being the most prominent one. Recruitment of p300 to p53 is pivotal in the regulation of p53-dependent genes. Emerging evidence suggests that p300 adopts an active conformation upon binding to the tetrameric p53, resulting in its enhanced acetylation activity. As a modular protein, p300 consists of multiple well-defined domains, where the structured domains are interlinked with unstructured linker regions. A crystal structure of the central domain of p300 encompassing Bromo, RING, PHD, and HAT domains demonstrates a compact module, where the HAT active site stays occluded by the RING domain. However, although p300 has a significant role in mediating the transcriptional activity of p53, only a few structural details on the complex of these two full-length proteins are available. Here, we present a cryo-electron microscopy (cryo-EM) study on the p300-p53 complex. The three-dimensional cryo-EM density map of the p300-p53 complex, when compared to the cryo-EM map of free p300, revealed that substantial change in the relative arrangement of Bromo and HAT domains occurs upon complex formation, which is likely required for exposing HAT active site and subsequent acetyltransferase activity. Our observation correlates well with previous studies showing that the presence of Bromodomain is obligatory for effective acetyltransferase activity of HAT. Thus, our result sheds new light on the mechanism whereby p300, following binding with p53, gets activated. | ||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 5xzc.cif.gz | 67.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb5xzc.ent.gz | 37.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 5xzc.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/xz/5xzc ftp://data.pdbj.org/pub/pdb/validation_reports/xz/5xzc | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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詳細 | One molecule of p300 interacts with four molecules of p53 (i.e, p300 monomer interacts with p53 tetramer) |
-要素
#1: タンパク質 | 分子量: 72100.062 Da / 分子数: 1 / 断片: UNP residues 1046-1664 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EP300, P300 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: Q09472, ヒストンアセチルトランスフェラーゼ |
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#2: タンパク質 | 分子量: 29898.908 Da / 分子数: 4 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: TP53, P53 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P04637 |
-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 |
-試料調製
構成要素 | 名称: p300-p53 complex / タイプ: COMPLEX 詳細: Proteins were purified separately and then complex was made for cryo-EM. Entity ID: all / 由来: MULTIPLE SOURCES | |||||||||||||||||||||||||||||||||||
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由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||||||||||||||||||||||
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) | |||||||||||||||||||||||||||||||||||
緩衝液 | pH: 7.5 | |||||||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 279 K |
-電子顕微鏡撮影
実験機器 | モデル: Tecnai Polara / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI POLARA 300 |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 59000 X / 倍率(補正後): 78894 X / 最大 デフォーカス(公称値): 4500 nm / 最小 デフォーカス(公称値): 1700 nm / Calibrated defocus min: 1700 nm / 最大 デフォーカス(補正後): 4500 nm / Cs: 2 mm / C2レンズ絞り径: 150 µm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: GATAN 910 MULTI-SPECIMEN SINGLE TILT CRYO TRANSFER HOLDER |
撮影 | 平均露光時間: 1 sec. / 電子線照射量: 15 e/Å2 / フィルム・検出器のモデル: FEI EAGLE (4k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 10.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 10088 / アルゴリズム: BACK PROJECTION / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 |
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原子モデル構築 | Source name: PDB / タイプ: experimental model
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精密化 | 最高解像度: 10.7 Å |