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基本情報
登録情報 | データベース: PDB / ID: 9eoz | ||||||||||||||||||
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タイトル | Human OGG1 bound to a nucleosome core particle with 8-oxodGuo lesion at SHL6.0 | ||||||||||||||||||
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![]() | DNA BINDING PROTEIN / hOGG1 / 8-oxoguanine / nucleosome / base excision repair | ||||||||||||||||||
機能・相同性 | ![]() Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / negative regulation of chromosome condensation / depyrimidination / Barr body ...Defective OGG1 Substrate Binding / Defective OGG1 Substrate Processing / Defective OGG1 Localization / depurination / negative regulation of double-strand break repair via single-strand annealing / oxidized purine nucleobase lesion DNA N-glycosylase activity / base-excision repair, AP site formation / negative regulation of chromosome condensation / depyrimidination / Barr body / regulation of centromere complex assembly / 8-oxo-7,8-dihydroguanine DNA N-glycosylase activity / Displacement of DNA glycosylase by APEX1 / positive regulation of gene expression via chromosomal CpG island demethylation / pericentric heterochromatin formation / inner kinetochore / response to folic acid / muscle cell differentiation / oocyte maturation / oxidized purine DNA binding / 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素 / nucleosomal DNA binding / cellular response to cadmium ion / APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway / nucleus organization / spermatid development / response to light stimulus / single fertilization / negative regulation of megakaryocyte differentiation / subtelomeric heterochromatin formation / protein localization to CENP-A containing chromatin / RNA polymerase II core promoter sequence-specific DNA binding / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Deposition of new CENPA-containing nucleosomes at the centromere / embryo implantation / telomere organization / Inhibition of DNA recombination at telomere / Meiotic synapsis / RNA Polymerase I Promoter Opening / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / Assembly of the ORC complex at the origin of replication / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / innate immune response in mucosa / SUMOylation of chromatin organization proteins / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / SIRT1 negatively regulates rRNA expression / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / nucleotide-excision repair / cellular response to reactive oxygen species / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / response to radiation / G2/M DNA damage checkpoint / HDMs demethylate histones / NoRC negatively regulates rRNA expression / base-excision repair / multicellular organism growth / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / nuclear matrix / Transcriptional regulation of granulopoiesis / HCMV Early Events / antimicrobial humoral immune response mediated by antimicrobial peptide / male gonad development / osteoblast differentiation / structural constituent of chromatin / antibacterial humoral response / UCH proteinases / nucleosome / heterochromatin formation / E3 ubiquitin ligases ubiquitinate target proteins / nucleosome assembly / response to estradiol / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization 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: 3.1 Å | ||||||||||||||||||
![]() | Ren, M. / Gut, F. / Fan, Y. / Hopfner, K.-P. / Zhou, C. | ||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Structural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles. 著者: Mengtian Ren / Fabian Gut / Yilan Fan / Jingke Ma / Xiajing Shan / Aysenur Yikilmazsoy / Mariia Likhodeeva / Karl-Peter Hopfner / Chuanzheng Zhou / ![]() ![]() 要旨: Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. ...Base excision repair (BER) is initialized by DNA glycosylases, which recognize and flip damaged bases out of the DNA duplex into the enzymes active site, followed by cleavage of the glycosidic bond. Recent studies have revealed that all types of DNA glycosylases repair base lesions less efficiently within nucleosomes, and their repair activity is highly depended on the lesion's location within the nucleosome. To reveal the underlying molecular mechanism of this phenomenon, we determine the 3.1 Å cryo-EM structure of human 8-oxoguanine-DNA glycosylase 1 (hOGG1) bound to a nucleosome core particle (NCP) containing a common oxidative base lesion, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Our structural analysis shows that hOGG1 can recognize and flip 8-oxodGuo even within NCPs; however, the interaction between 8-oxodGuo and hOGG1 in a NCP context is weaker than in free DNA due to competition for nucleosomal DNA by the histones. Binding of OGG1 and the flipping of 8-oxodGuo by hOGG1 leads to a partial detachment of DNA from the histone core and a ratchet-like inward movement of nucleosomal DNA. Our findings provide insights into how the dynamic structure of nucleosomes modulate the activity of repair enzymes within chromatin. | ||||||||||||||||||
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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 | ![]() | 376.7 KB | 表示 | ![]() |
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PDB形式 | ![]() | 283.7 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 |
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-関連構造データ
関連構造データ | ![]() 19870MC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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 , 5種, 9分子 ABFEKGLHM
#1: タンパク質 | 分子量: 40092.289 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() 参照: UniProt: O15527, 加水分解酵素; 糖加水分解酵素; N-グリコシル化合物加水分解酵素, DNA-(apurinic or apyrimidinic site) lyase | ||||||
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#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: 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 発現宿主: ![]() ![]() #3: タンパク質 | 分子量: 15229.787 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: H3-3A, H3.3A, H3F3, H3F3A, PP781, H3-3B, H3.3B, H3F3B 発現宿主: ![]() ![]() #4: タンパク質 | 分子量: 14004.329 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #5: 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: HIST1H2BC, H2BFL, HIST1H2BE, H2BFH, HIST1H2BF, H2BFG, HIST1H2BG, H2BFA, HIST1H2BI, H2BFK 発現宿主: ![]() ![]() |
-Widom 601 DNA (145- ... , 2種, 2分子 YZ
#6: DNA鎖 | 分子量: 44520.383 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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#7: DNA鎖 | 分子量: 45007.660 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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Has protein modification | N |
-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 |
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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: 7.5 | ||||||||||||||||||||||||
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: BRIGHT FIELD / 最大 デフォーカス(公称値): 2900 nm / 最小 デフォーカス(公称値): 1100 nm |
撮影 | 電子線照射量: 43.76 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.21.1_5286: / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 66370 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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