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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7u52 | |||||||||
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タイトル | nucleosome core particle with AP-site at SHL-6.5 | |||||||||
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![]() | DNA BINDING PROTEIN/DNA / nucleosome / DNA damage / DNA repair / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex | |||||||||
機能・相同性 | ![]() Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation ...Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / 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 / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Interleukin-7 signaling / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / 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 / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / E3 ubiquitin ligases ubiquitinate target proteins / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / antibacterial humoral response / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / enzyme binding / DNA binding / extracellular space / extracellular exosome / extracellular region / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() 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: 3.4 Å | |||||||||
![]() | Freudenthal, B.D. / Weaver, T.M. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for APE1 processing DNA damage in the nucleosome. 著者: Tyler M Weaver / Nicole M Hoitsma / Jonah J Spencer / Lokesh Gakhar / Nicholas J Schnicker / Bret D Freudenthal / ![]() 要旨: Genomic DNA is continually exposed to endogenous and exogenous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes, which present a barrier to accessing and ...Genomic DNA is continually exposed to endogenous and exogenous factors that promote DNA damage. Eukaryotic genomic DNA is packaged into nucleosomes, which present a barrier to accessing and effectively repairing DNA damage. The mechanisms by which DNA repair proteins overcome this barrier to repair DNA damage in the nucleosome and protect genomic stability is unknown. Here, we determine how the base excision repair (BER) endonuclease AP-endonuclease 1 (APE1) recognizes and cleaves DNA damage in the nucleosome. Kinetic assays determine that APE1 cleaves solvent-exposed AP sites in the nucleosome with 3 - 6 orders of magnitude higher efficiency than occluded AP sites. A cryo-electron microscopy structure of APE1 bound to a nucleosome containing a solvent-exposed AP site reveal that APE1 uses a DNA sculpting mechanism for AP site recognition, where APE1 bends the nucleosomal DNA to access the AP site. Notably, additional biochemical and structural characterization of occluded AP sites identify contacts between the nucleosomal DNA and histone octamer that prevent efficient processing of the AP site by APE1. These findings provide a rationale for the position-dependent activity of BER proteins in the nucleosome and suggests the ability of BER proteins to sculpt nucleosomal DNA drives efficient BER in chromatin. | |||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 324.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 243 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 910.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 925.7 KB | 表示 | |
XML形式データ | ![]() | 33.9 KB | 表示 | |
CIF形式データ | ![]() | 52.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-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
-タンパク質 , 4種, 8分子 AEBFCGDH
#1: タンパク質 | 分子量: 15257.838 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: H3C15, HIST2H3A, H3C14, H3F2, H3FM, HIST2H3C, H3C13, HIST2H3D 発現宿主: ![]() ![]() #2: タンパク質 | 分子量: 11263.231 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: ![]() ![]() #3: タンパク質 | 分子量: 13990.342 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: H2AC11, H2AFP, HIST1H2AG, H2AC13, H2AFC, HIST1H2AI, H2AC15, H2AFD, HIST1H2AK, H2AC16, H2AFI, HIST1H2AL, H2AC17, H2AFN, HIST1H2AM 発現宿主: ![]() ![]() #4: タンパク質 | 分子量: 13806.018 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: H2BC4, H2BFL, HIST1H2BC, H2BC6, H2BFH, HIST1H2BE, H2BC7, H2BFG, HIST1H2BF, H2BC8, H2BFA, HIST1H2BG, H2BC10, H2BFK, HIST1H2BI 発現宿主: ![]() ![]() |
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-DNA鎖 , 2種, 2分子 IJ
#5: DNA鎖 | 分子量: 45029.684 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: 45610.043 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) synthetic construct (人工物) |
-詳細
研究の焦点であるリガンドがあるか | Y |
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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: nucleosome core particle with AP-site at SHL-6.5 / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT | ||||||||||||||||||||
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分子量 | 実験値: NO | ||||||||||||||||||||
由来(天然) | 生物種: ![]() | ||||||||||||||||||||
由来(組換発現) | 生物種: ![]() ![]() | ||||||||||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||||||||||
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 | ||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R2/2 | ||||||||||||||||||||
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: BRIGHT FIELD / 最大 デフォーカス(公称値): 2100 nm / 最小 デフォーカス(公称値): 700 nm |
撮影 | 電子線照射量: 47 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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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: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 96407 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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