+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ham | ||||||
---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the CBP catalytic core bound to the H4K12acK16ac nucleosome, class 2 | ||||||
要素 |
| ||||||
キーワード | TRANSFERASE/DNA / Acetyl taransferase / Complex / Nucleosome / TRANSFERASE / TRANSFERASE-DNA complex | ||||||
機能・相同性 | 機能・相同性情報 peptide lactyltransferase (CoA-dependent) activity / regulation of smoothened signaling pathway / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production ...peptide lactyltransferase (CoA-dependent) activity / regulation of smoothened signaling pathway / NFE2L2 regulating ER-stress associated genes / peptide N-acetyltransferase activity / Activation of the TFAP2 (AP-2) family of transcription factors / NFE2L2 regulating inflammation associated genes / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / NFE2L2 regulates pentose phosphate pathway genes / NFE2L2 regulating MDR associated enzymes / MRF binding / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / Regulation of FOXO transcriptional activity by acetylation / Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / RUNX3 regulates NOTCH signaling / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / FOXO-mediated transcription of cell death genes / Regulation of NFE2L2 gene expression / negative regulation of transcription by RNA polymerase I / NOTCH3 Intracellular Domain Regulates Transcription / TRAF6 mediated IRF7 activation / peptide-lysine-N-acetyltransferase activity / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / embryonic digit morphogenesis / homeostatic process / protein acetylation / Notch-HLH transcription pathway / positive regulation of transforming growth factor beta receptor signaling pathway / Formation of paraxial mesoderm / stimulatory C-type lectin receptor signaling pathway / acetyltransferase activity / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / histone acetyltransferase complex / negative regulation of tumor necrosis factor-mediated signaling pathway / Attenuation phase / positive regulation of double-strand break repair via homologous recombination / cellular response to nutrient levels / protein localization to CENP-A containing chromatin / Transcriptional and post-translational regulation of MITF-M expression and activity / canonical NF-kappaB signal transduction / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / histone acetyltransferase activity / Packaging Of Telomere Ends / regulation of cellular response to heat / histone acetyltransferase / 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 / nucleosomal DNA binding / 転移酵素; アシル基を移すもの; アミノアシル基以外のアシル基を移すもの / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / RORA activates gene expression / Inhibition of DNA recombination at telomere / Regulation of lipid metabolism by PPARalpha / NPAS4 regulates expression of target genes / telomere organization / Meiotic synapsis / CD209 (DC-SIGN) signaling / Interleukin-7 signaling / RNA Polymerase I Promoter Opening / epigenetic regulation of gene expression / Assembly of the ORC complex at the origin of replication / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / BMAL1:CLOCK,NPAS2 activates circadian gene expression / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / Condensation of Prophase Chromosomes / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / lipopolysaccharide binding / Transcriptional regulation by small RNAs / protein destabilization / Formation of the beta-catenin:TCF transactivating complex / Heme signaling / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / Transcriptional activation of mitochondrial biogenesis / G2/M DNA damage checkpoint / HDMs demethylate histones 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: 4.5 Å | ||||||
データ登録者 | Kikuchi, M. / Morita, S. / Wakamori, M. / Shin, S. / Uchikubo-Kamo, T. / Shirouzu, M. / Umehara, T. | ||||||
資金援助 | 日本, 1件
| ||||||
引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Epigenetic mechanisms to propagate histone acetylation by p300/CBP. 著者: Masaki Kikuchi / Satoshi Morita / Masatoshi Wakamori / Shin Sato / Tomomi Uchikubo-Kamo / Takehiro Suzuki / Naoshi Dohmae / Mikako Shirouzu / Takashi Umehara / 要旨: Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which ...Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket responsible for reading, but also interacted with the DNA minor grooves via the outside of that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. The primary target that p300 writes by reading H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation from the nucleosome. We propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer to inherit epigenetic storage, and transcribes it from the H3-H4 tetramer to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization. | ||||||
履歴 |
|
-構造の表示
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 | 8ham.cif.gz | 412.9 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb8ham.ent.gz | 308 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8ham.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
文書・要旨 | 8ham_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 8ham_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 8ham_validation.xml.gz | 51.9 KB | 表示 | |
CIF形式データ | 8ham_validation.cif.gz | 83.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ha/8ham ftp://data.pdbj.org/pub/pdb/validation_reports/ha/8ham | HTTPS FTP |
-関連構造データ
関連構造データ | 34596MC 8hagC 8hahC 8haiC 8hajC 8hakC 8halC 8hanC 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) |
---|---|
類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
-タンパク質 , 5種, 9分子 AEBFCGDHK
#1: タンパク質 | 分子量: 15305.969 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, 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: Escherichia coli (大腸菌) / 参照: UniProt: P68431 #2: タンパク質 | 分子量: 11345.289 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Escherichia coli (大腸菌) #3: タンパク質 | 分子量: 14034.355 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: H2AC4, H2AFM, HIST1H2AB, H2AC8, H2AFA, HIST1H2AE / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P04908 #4: タンパク質 | 分子量: 13804.045 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: H2BC11, H2BFR, HIST1H2BJ / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P06899 #6: タンパク質 | | 分子量: 92690.906 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: CREBBP, CBP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) 参照: UniProt: Q92793, histone acetyltransferase, 転移酵素; アシル基を移すもの; アミノアシル基以外のアシル基を移すもの |
---|
-DNA鎖 , 1種, 2分子 IJ
#5: DNA鎖 | 分子量: 55560.527 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: Escherichia coli (大腸菌) |
---|
-詳細
研究の焦点であるリガンドがあるか | Y |
---|---|
Has protein modification | Y |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 | 名称: the CBP catalytic core bound to the H4K12acK16ac nucleosome タイプ: COMPLEX / 詳細: CBP was expressed in insect cells. / Entity ID: all / 由来: RECOMBINANT |
---|---|
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: 7.2 |
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 |
-電子顕微鏡撮影
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TECNAI ARCTICA |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 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): 1700 nm / 最小 デフォーカス(公称値): 900 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 90318 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 256.28 Å2 | ||||||||||||||||||||||||
拘束条件 |
|