+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7xzz | |||||||||||||||||||||||||||||||||
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タイトル | Cryo-EM structure of the nucleosome in complex with p53 | |||||||||||||||||||||||||||||||||
要素 |
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キーワード | GENE REGULATION/DNA / Transcription factor / Tumor-suppressor / GENE REGULATION-DNA COMPLEX | |||||||||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 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 ...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 / 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 / positive regulation of mitochondrial membrane permeability / negative regulation of mitophagy / positive regulation of programmed necrotic cell death / mRNA transcription / bone marrow development / circadian behavior / histone deacetylase regulator activity / germ cell nucleus / regulation of mitochondrial membrane permeability involved in apoptotic process / RUNX3 regulates CDKN1A transcription / 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 / TP53 Regulates Transcription of Death Receptors and Ligands / Activation of PUMA and translocation to mitochondria / DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / Regulation of TP53 Activity through Association with Co-factors / mitochondrial DNA repair / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / T cell lineage commitment / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / ER overload response / negative regulation of DNA replication / B cell lineage commitment / positive regulation of cardiac muscle cell apoptotic process / thymocyte apoptotic process / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TP53 Regulates Transcription of Caspase Activators and Caspases / mitotic G1 DNA damage checkpoint signaling / cardiac septum morphogenesis / positive regulation of execution phase of apoptosis / entrainment of circadian clock by photoperiod / PI5P Regulates TP53 Acetylation / Association of TriC/CCT with target proteins during biosynthesis / Zygotic genome activation (ZGA) / necroptotic process / protein localization to CENP-A containing chromatin / positive regulation of release of cytochrome c from mitochondria / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / rRNA transcription / TFIID-class transcription factor complex binding / negative regulation of telomere maintenance via telomerase / CENP-A containing nucleosome / SUMOylation of transcription factors / intrinsic apoptotic signaling pathway by p53 class mediator / general transcription initiation factor binding / mitophagy / Transcriptional Regulation by VENTX / DNA damage response, signal transduction by p53 class mediator / response to X-ray / replicative senescence / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / negative regulation of tumor necrosis factor-mediated signaling pathway / cellular response to UV-C / : / neuroblast proliferation / negative regulation of reactive oxygen species metabolic process / hematopoietic stem cell differentiation / Replacement of protamines by nucleosomes in the male pronucleus / chromosome organization / positive regulation of RNA polymerase II transcription preinitiation complex assembly / arachidonate 15-lipoxygenase / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / arachidonate 15-lipoxygenase activity / T cell proliferation involved in immune response / Packaging Of Telomere Ends / glial cell proliferation / Pyroptosis / cis-regulatory region sequence-specific DNA binding / embryonic organ development / lipoxygenase pathway / hematopoietic progenitor cell differentiation / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / cellular response to actinomycin D / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation 類似検索 - 分子機能 | |||||||||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) synthetic construct (人工物) | |||||||||||||||||||||||||||||||||
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: 4.07 Å | |||||||||||||||||||||||||||||||||
データ登録者 | Nishimura, M. / Nozawa, K. / Takizawa, Y. / Kurumizaka, H. | |||||||||||||||||||||||||||||||||
資金援助 | 日本, 10件
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引用 | ジャーナル: PNAS Nexus / 年: 2022 タイトル: Structural basis for p53 binding to its nucleosomal target DNA sequence. 著者: Masahiro Nishimura / Yoshimasa Takizawa / Kayo Nozawa / Hitoshi Kurumizaka / 要旨: The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome ...The tumor suppressor p53 functions as a pioneer transcription factor that binds a nucleosomal target DNA sequence. However, the mechanism by which p53 binds to its target DNA in the nucleosome remains elusive. Here we report the cryo-electron microscopy structures of the p53 DNA-binding domain and the full-length p53 protein complexed with a nucleosome containing the 20 base-pair target DNA sequence of p53 (p53BS). In the p53-nucleosome structures, the p53 DNA-binding domain forms a tetramer and specifically binds to the p53BS DNA, located near the entry/exit region of the nucleosome. The nucleosomal position of the p53BS DNA is within the genomic p21 promoter region. The p53 binding peels the DNA from the histone surface, and drastically changes the DNA path around the p53BS on the nucleosome. The C-terminal domain of p53 also binds to the DNA around the center and linker DNA regions of the nucleosome, as revealed by hydroxyl radical footprinting. These results provide important structural information for understanding the mechanism by which p53 binds the nucleosome and changes the chromatin structure for gene activation. | |||||||||||||||||||||||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7xzz.cif.gz | 456.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7xzz.ent.gz | 350.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7xzz.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/7xzz ftp://data.pdbj.org/pub/pdb/validation_reports/xz/7xzz | 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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1 |
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-要素
-タンパク質 , 5種, 12分子 AEBFCGDHKLMN
#1: タンパク質 | 分子量: 15719.445 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: H3C1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P68431 #2: タンパク質 | 分子量: 11676.703 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: H4C1 / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P62805 #3: タンパク質 | 分子量: 14447.825 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: HIST1H2AE / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P04908 #4: タンパク質 | 分子量: 14217.516 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: HIST1H2BJ / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P06899 #7: タンパク質 | 分子量: 43855.297 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 |
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-DNA鎖 , 2種, 2分子 IJ
#5: DNA鎖 | 分子量: 52032.137 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) |
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#6: DNA鎖 | 分子量: 52312.316 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) |
-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 |
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分子量 | 値: 0.398 MDa / 実験値: NO | ||||||||||||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||||||
由来(組換発現) | 生物種: Escherichia coli (大腸菌) | ||||||||||||||||||||||||
緩衝液 | pH: 8 | ||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.25 mg/ml / 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: 289.15 K |
-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: 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 FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k 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 | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 2739901 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4.07 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 92142 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | 空間: REAL | ||||||||||||||||||||||||||||||||||||
原子モデル構築 |
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