+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6r91 | ||||||||||||||||||||||||
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タイトル | Cryo-EM structure of NCP_THF2(-3)-UV-DDB | ||||||||||||||||||||||||
要素 |
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キーワード | DNA BINDING PROTEIN (DNA結合タンパク質) / DNA damage (DNA修復) / Nucleosome (ヌクレオソーム) / 6-4 photoproduct | ||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex ...positive regulation by virus of viral protein levels in host cell / epigenetic programming in the zygotic pronuclei / spindle assembly involved in female meiosis / Cul4-RING E3 ubiquitin ligase complex / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / negative regulation of reproductive process / negative regulation of developmental process / site of DNA damage / cullin family protein binding / viral release from host cell / pyrimidine dimer repair / negative regulation of tumor necrosis factor-mediated signaling pathway / ectopic germ cell programmed cell death / negative regulation of megakaryocyte differentiation / positive regulation of viral genome replication / protein autoubiquitination / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / epigenetic regulation of gene expression / Packaging Of Telomere Ends / response to UV / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / positive regulation of gluconeogenesis / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / SUMOylation of chromatin organization proteins / Assembly of the ORC complex at the origin of replication / DNAメチル化 / Condensation of Prophase Chromosomes / HCMV Late Events / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / proteasomal protein catabolic process / Recognition of DNA damage by PCNA-containing replication complex / nucleotide-excision repair / RNA Polymerase I Promoter Escape / TP53 Regulates Transcription of DNA Repair Genes / Nonhomologous End-Joining (NHEJ) / lipopolysaccharide binding / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / DNA Damage Recognition in GG-NER / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / B-WICH complex positively regulates rRNA expression / Dual Incision in GG-NER / HDMs demethylate histones / regulation of circadian rhythm / DNA Damage/Telomere Stress Induced Senescence / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Metalloprotease DUBs / Formation of TC-NER Pre-Incision Complex / PKMTs methylate histone lysines / RMTs methylate histone arginines / Wntシグナル経路 / 遺伝的組換え / Pre-NOTCH Transcription and Translation / Formation of Incision Complex in GG-NER / nucleosome assembly / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Dual incision in TC-NER / protein polyubiquitination / Gap-filling DNA repair synthesis and ligation in TC-NER / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / positive regulation of protein catabolic process / UCH proteinases / cellular response to UV / rhythmic process / ヌクレオソーム / antimicrobial humoral immune response mediated by antimicrobial peptide / protein-macromolecule adaptor activity / E3 ubiquitin ligases ubiquitinate target proteins / site of double-strand break / 細胞結合 / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / 遺伝子発現 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: 4.1 Å | ||||||||||||||||||||||||
データ登録者 | Matsumoto, S. / Cavadini, S. / Bunker, R.D. / Thoma, N.H. | ||||||||||||||||||||||||
資金援助 | スイス, 日本, 7件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: DNA damage detection in nucleosomes involves DNA register shifting. 著者: Syota Matsumoto / Simone Cavadini / Richard D Bunker / Ralph S Grand / Alessandro Potenza / Julius Rabl / Junpei Yamamoto / Andreas D Schenk / Dirk Schübeler / Shigenori Iwai / Kaoru ...著者: Syota Matsumoto / Simone Cavadini / Richard D Bunker / Ralph S Grand / Alessandro Potenza / Julius Rabl / Junpei Yamamoto / Andreas D Schenk / Dirk Schübeler / Shigenori Iwai / Kaoru Sugasawa / Hitoshi Kurumizaka / Nicolas H Thomä / 要旨: Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced ...Access to DNA packaged in nucleosomes is critical for gene regulation, DNA replication and DNA repair. In humans, the UV-damaged DNA-binding protein (UV-DDB) complex detects UV-light-induced pyrimidine dimers throughout the genome; however, it remains unknown how these lesions are recognized in chromatin, in which nucleosomes restrict access to DNA. Here we report cryo-electron microscopy structures of UV-DDB bound to nucleosomes bearing a 6-4 pyrimidine-pyrimidone dimer or a DNA-damage mimic in various positions. We find that UV-DDB binds UV-damaged nucleosomes at lesions located in the solvent-facing minor groove without affecting the overall nucleosome architecture. In the case of buried lesions that face the histone core, UV-DDB changes the predominant translational register of the nucleosome and selectively binds the lesion in an accessible, exposed position. Our findings explain how UV-DDB detects occluded lesions in strongly positioned nucleosomes, and identify slide-assisted site exposure as a mechanism by which high-affinity DNA-binding proteins can access otherwise occluded sites in nucleosomal DNA. | ||||||||||||||||||||||||
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 | 6r91.cif.gz | 877.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6r91.ent.gz | 716.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6r91.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/r9/6r91 ftp://data.pdbj.org/pub/pdb/validation_reports/r9/6r91 | HTTPS FTP |
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-関連構造データ
関連構造データ | 4765MC 4762C 4763C 4764C 4766C 4767C 4768C 6r8yC 6r8zC 6r90C 6r92C 6r93C 6r94C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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-要素
-タンパク質 , 4種, 8分子 AEBFCGDH
#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: HIST1H3A, H3FA, HIST1H3B, H3FL, HIST1H3C, H3FC, HIST1H3D, H3FB, HIST1H3E, H3FD, HIST1H3F, H3FI, HIST1H3G, H3FH, HIST1H3H, H3FK, HIST1H3I, H3FF, HIST1H3J, H3FJ 発現宿主: Escherichia coli BL21(DE3) (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: HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, ...遺伝子: HIST1H4A, H4/A, H4FA, HIST1H4B, H4/I, H4FI, HIST1H4C, H4/G, H4FG, HIST1H4D, H4/B, H4FB, HIST1H4E, H4/J, H4FJ, HIST1H4F, H4/C, H4FC, HIST1H4H, H4/H, H4FH, HIST1H4I, H4/M, H4FM, HIST1H4J, H4/E, H4FE, HIST1H4K, H4/D, H4FD, HIST1H4L, H4/K, H4FK, HIST2H4A, H4/N, H4F2, H4FN, HIST2H4, HIST2H4B, H4/O, H4FO, HIST4H4 細胞株 (発現宿主): JM109(DE3) / 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: HIST1H2AB, H2AFM, HIST1H2AE, H2AFA / 発現宿主: Escherichia coli BL21(DE3) (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, H2BFR / 発現宿主: Escherichia coli BL21(DE3) (大腸菌) / 参照: UniProt: P06899 |
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-Human alpha-satellite DNA (145- ... , 2種, 2分子 IJ
#5: DNA鎖 | 分子量: 44756.648 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) |
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#6: DNA鎖 | 分子量: 44452.434 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) |
-DNA damage-binding protein ... , 2種, 2分子 KL
#7: タンパク質 | 分子量: 129766.305 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DDB1, XAP1 / 細胞株 (発現宿主): High five / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q16531 |
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#8: タンパク質 | 分子量: 50601.844 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DDB2 / 細胞株 (発現宿主): High five / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q92466 |
-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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由来(天然) |
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由来(組換発現) |
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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 / 湿度: 85 % / 凍結前の試料温度: 277 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: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 119309 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL / Target criteria: Cross-correlation coefficient | ||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 |
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