+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 5xzc | ||||||
---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of p300-p53 protein complex | ||||||
![]() |
| ||||||
![]() | TRANSCRIPTION / transcription factor / autoacetylation / allosteric interaction / catalytically active form | ||||||
機能・相同性 | ![]() behavioral defense response / negative regulation of protein oligomerization / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / swimming / peptide butyryltransferase activity / regulation of tubulin deacetylation ...behavioral defense response / negative regulation of protein oligomerization / peptidyl-lysine propionylation / histone lactyltransferase (CoA-dependent) activity / peptidyl-lysine crotonylation / peptidyl-lysine butyrylation / histone butyryltransferase activity / swimming / peptide butyryltransferase activity / regulation of tubulin deacetylation / histone H2B acetyltransferase activity / internal protein amino acid acetylation / peptide 2-hydroxyisobutyryltransferase activity / histone crotonyltransferase activity / thigmotaxis / protein propionyltransferase activity / NOTCH2 intracellular domain regulates transcription / L-lysine N-acetyltransferase activity, acting on acetyl phosphate as donor / positive regulation of TORC2 signaling / internal peptidyl-lysine acetylation / histone H4 acetyltransferase activity / cellular response to L-leucine / histone H3 acetyltransferase activity / NFE2L2 regulating ER-stress associated genes / protein N-acetyltransferase activity / acetylation-dependent protein binding / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / NGF-stimulated transcription / N-terminal peptidyl-lysine acetylation / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / STAT3 nuclear events downstream of ALK signaling / Polo-like kinase mediated events / NFE2L2 regulating MDR associated enzymes / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / host-mediated activation of viral transcription / TGFBR3 expression / negative regulation of helicase activity / 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 / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of androgen receptor signaling pathway / regulation of cell cycle G2/M phase transition / regulation of fibroblast apoptotic process / intrinsic apoptotic signaling pathway in response to hypoxia / oligodendrocyte apoptotic process / negative regulation of miRNA processing / regulation of mitochondrion organization / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / glucose catabolic process to lactate via pyruvate / positive regulation of mitochondrial membrane permeability / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Regulation of FOXO transcriptional activity by acetylation / RUNX3 regulates NOTCH signaling / circadian behavior / regulation of mitochondrial membrane permeability involved in apoptotic process / germ cell nucleus / NOTCH4 Intracellular Domain Regulates Transcription / Nuclear events mediated by NFE2L2 / RUNX3 regulates CDKN1A transcription / face morphogenesis / Regulation of NFE2L2 gene expression / Regulation of gene expression by Hypoxia-inducible Factor / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / regulation of DNA damage response, signal transduction by p53 class mediator / platelet formation / NOTCH3 Intracellular Domain Regulates Transcription / regulation of glycolytic process / histone deacetylase regulator activity / TRAF6 mediated IRF7 activation / negative regulation of glial cell proliferation / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / Regulation of TP53 Activity through Association with Co-factors / negative regulation of neuroblast proliferation / megakaryocyte development / protein-lysine-acetyltransferase activity / T cell lineage commitment / STAT family protein binding / nuclear androgen receptor binding / acyltransferase activity / mitochondrial DNA repair / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / protein acetylation / ER overload response / B cell lineage commitment 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: 10.7 Å | ||||||
![]() | Ghosh, R. / Roy, S. / Sengupta, J. | ||||||
![]() | ![]() 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 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 67.2 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 37.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
---|
-関連構造データ
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 | ![]()
|
2 | ![]()
|
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) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q09472, histone acetyltransferase |
---|---|
#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) ![]() ![]() ![]() |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 | |||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
由来(天然) | 生物種: ![]() | |||||||||||||||||||||||||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | |||||||||||||||||||||||||||||||||||
緩衝液 | pH: 7.5 | |||||||||||||||||||||||||||||||||||
緩衝液成分 |
| |||||||||||||||||||||||||||||||||||
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 |
---|---|
顕微鏡 | モデル: FEI POLARA 300 |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | Source name: PDB / タイプ: experimental model
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
精密化 | 最高解像度: 10.7 Å |