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基本情報
登録情報 | データベース: PDB / ID: 7scy | ||||||
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タイトル | Nuc147 bound to single BRCT | ||||||
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![]() | DNA BINDING PROTEIN/DNA / PARP1 / BRCT / nucleosome / DNA BINDING PROTEIN-DNA complex | ||||||
機能・相同性 | ![]() NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / regulation of base-excision repair / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / carbohydrate biosynthetic process / positive regulation of single strand break repair ...NAD+-histone H2BS6 serine ADP-ribosyltransferase activity / NAD+-histone H3S10 serine ADP-ribosyltransferase activity / NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activity / regulation of base-excision repair / positive regulation of myofibroblast differentiation / negative regulation of ATP biosynthetic process / NAD+-protein-tyrosine ADP-ribosyltransferase activity / NAD+-protein-histidine ADP-ribosyltransferase activity / carbohydrate biosynthetic process / positive regulation of single strand break repair / regulation of circadian sleep/wake cycle, non-REM sleep / vRNA Synthesis / negative regulation of adipose tissue development / NAD+-protein-serine ADP-ribosyltransferase activity / regulation of catalytic activity / NAD DNA ADP-ribosyltransferase activity / NAD+-protein-aspartate ADP-ribosyltransferase activity / NAD+-protein-glutamate ADP-ribosyltransferase activity / DNA ADP-ribosylation / mitochondrial DNA metabolic process / regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / signal transduction involved in regulation of gene expression / positive regulation of necroptotic process / ATP generation from poly-ADP-D-ribose / replication fork reversal / transcription regulator activator activity / HDR through MMEJ (alt-NHEJ) / R-SMAD binding / positive regulation of DNA-templated transcription, elongation / positive regulation of intracellular estrogen receptor signaling pathway / NAD+ ADP-ribosyltransferase / cellular response to zinc ion / negative regulation of telomere maintenance via telomere lengthening / protein auto-ADP-ribosylation / response to aldosterone / mitochondrial DNA repair / positive regulation of mitochondrial depolarization / negative regulation of cGAS/STING signaling pathway / protein poly-ADP-ribosylation / positive regulation of cardiac muscle hypertrophy / negative regulation of transcription elongation by RNA polymerase II / nuclear replication fork / NAD+-protein ADP-ribosyltransferase activity / site of DNA damage / protein localization to CENP-A containing chromatin / positive regulation of SMAD protein signal transduction / CENP-A containing nucleosome / macrophage differentiation / protein autoprocessing / decidualization / NAD+-protein poly-ADP-ribosyltransferase activity / 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの / positive regulation of double-strand break repair via homologous recombination / POLB-Dependent Long Patch Base Excision Repair / negative regulation of tumor necrosis factor-mediated signaling pathway / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / nucleosome binding / Packaging Of Telomere Ends / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / SUMOylation of DNA damage response and repair proteins / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / protein localization to chromatin / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / negative regulation of innate immune response / telomere maintenance / nucleotidyltransferase activity / Interleukin-7 signaling / epigenetic regulation of gene expression / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / transforming growth factor beta receptor signaling pathway / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / cellular response to nerve growth factor stimulus / Defective pyroptosis / mitochondrion organization / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape 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: 4.1 Å | ||||||
![]() | Muthurajan, U.M. / Rudolph, J.R. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer. 著者: Johannes Rudolph / Uma M Muthurajan / Megan Palacio / Jyothi Mahadevan / Genevieve Roberts / Annette H Erbse / Pamela N Dyer / Karolin Luger / ![]() 要旨: PARP1 is a key player in the response to DNA damage and is the target of clinical inhibitors for the treatment of cancers. Binding of PARP1 to damaged DNA leads to activation wherein PARP1 uses NAD ...PARP1 is a key player in the response to DNA damage and is the target of clinical inhibitors for the treatment of cancers. Binding of PARP1 to damaged DNA leads to activation wherein PARP1 uses NAD to add chains of poly(ADP-ribose) onto itself and other nuclear proteins. PARP1 also binds abundantly to intact DNA and chromatin, where it remains enzymatically inactive. We show that intact DNA makes contacts with the PARP1 BRCT domain, which was not previously recognized as a DNA-binding domain. This binding mode does not result in the concomitant reorganization and activation of the catalytic domain. We visualize the BRCT domain bound to nucleosomal DNA by cryogenic electron microscopy and identify a key motif conserved from ancestral BRCT domains for binding phosphates on DNA and phospho-peptides. Finally, we demonstrate that the DNA-binding properties of the BRCT domain contribute to the "monkey-bar mechanism" that mediates DNA transfer of PARP1. | ||||||
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構造ビューア | 分子: ![]() ![]() |
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-検証レポート
文書・要旨 | ![]() | 842.1 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 914.6 KB | 表示 | |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-DNA鎖 , 2種, 2分子 IJ
#1: DNA鎖 | 分子量: 45610.043 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
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#2: DNA鎖 | 分子量: 45138.770 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
-タンパク質 , 5種, 9分子 AEBFCGDHK
#3: 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) ![]() 遺伝子: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, ...遺伝子: H3C1, H3FA, HIST1H3A, H3C2, H3FL, HIST1H3B, H3C3, H3FC HIST1H3C, H3C4, H3FB, HIST1H3D, H3C6, H3FD, HIST1H3E, H3C7, H3FI, HIST1H3F, H3C8, H3FH, HIST1H3G, H3C10, H3FK, HIST1H3H, H3C11, H3FF, HIST1H3I, H3C12, H3FJ, HIST1H3J 発現宿主: ![]() ![]() #4: 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) ![]() 遺伝子: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...遺伝子: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4-16, HIST4H4 発現宿主: ![]() ![]() #5: 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) ![]() ![]() ![]() #6: 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) ![]() ![]() ![]() #7: タンパク質 | | 分子量: 14337.548 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() 参照: UniProt: P09874, NAD+ ADP-ribosyltransferase, 転移酵素; グリコシル基を移すもの; 五炭糖残基を移すもの |
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-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 |
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試料調製
構成要素 | 名称: Nuc147-PARP1-BRCT / タイプ: COMPLEX / Entity ID: all / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.214 MDa / 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 |
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 |
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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: ![]() |
電子レンズ | モード: OTHER |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
CTF補正 | タイプ: NONE |
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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: 16495 / 対称性のタイプ: POINT |