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Yorodumi- PDB-8ham: Cryo-EM structure of the CBP catalytic core bound to the H4K12acK... -
+Open data
-Basic information
Entry | Database: PDB / ID: 8ham | ||||||
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Title | Cryo-EM structure of the CBP catalytic core bound to the H4K12acK16ac nucleosome, class 2 | ||||||
Components |
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Keywords | TRANSFERASE/DNA / Acetyl taransferase / Complex / Nucleosome / TRANSFERASE / TRANSFERASE-DNA complex | ||||||
Function / homology | Function and homology information peptide lactyltransferase (CoA-dependent) activity / 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 / regulation of smoothened signaling pathway / histone H3K18 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity ...peptide lactyltransferase (CoA-dependent) activity / 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 / regulation of smoothened signaling pathway / histone H3K18 acetyltransferase activity / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / 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 gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells / Regulation of FOXO transcriptional activity by acetylation / RUNX3 regulates NOTCH signaling / Regulation of gene expression by Hypoxia-inducible Factor / Nuclear events mediated by NFE2L2 / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / negative regulation of transcription by RNA polymerase I / NOTCH3 Intracellular Domain Regulates Transcription / NFE2L2 regulating anti-oxidant/detoxification enzymes / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / peptide-lysine-N-acetyltransferase activity / FOXO-mediated transcription of cell death genes / 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 / acetyltransferase activity / stimulatory C-type lectin receptor signaling pathway / Zygotic genome activation (ZGA) / protein localization to CENP-A containing chromatin / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / CENP-A containing nucleosome / histone acetyltransferase complex / positive regulation of double-strand break repair via homologous recombination / negative regulation of tumor necrosis factor-mediated signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / Replacement of protamines by nucleosomes in the male pronucleus / Attenuation phase / Packaging Of Telomere Ends / cellular response to nutrient levels / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / Chromatin modifying enzymes / canonical NF-kappaB signal transduction / Deposition of new CENPA-containing nucleosomes at the centromere / regulation of cellular response to heat / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / histone acetyltransferase activity / Meiotic synapsis / histone acetyltransferase / Inhibition of DNA recombination at telomere / nucleosomal DNA binding / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / RNA Polymerase I Promoter Opening / RORA activates gene expression / NPAS4 regulates expression of target genes / Assembly of the ORC complex at the origin of replication / Regulation of lipid metabolism by PPARalpha / CD209 (DC-SIGN) signaling / Interleukin-7 signaling / epigenetic regulation of gene expression / 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 / BMAL1:CLOCK,NPAS2 activates circadian gene expression / PRC2 methylates histones and DNA / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / 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 / lipopolysaccharide binding / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / PPARA activates gene expression / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Heme signaling / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.5 Å | ||||||
Authors | Kikuchi, M. / Morita, S. / Wakamori, M. / Shin, S. / Uchikubo-Kamo, T. / Shirouzu, M. / Umehara, T. | ||||||
Funding support | Japan, 1items
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Citation | Journal: Nat Commun / Year: 2023 Title: Epigenetic mechanisms to propagate histone acetylation by p300/CBP. Authors: Masaki Kikuchi / Satoshi Morita / Masatoshi Wakamori / Shin Sato / Tomomi Uchikubo-Kamo / Takehiro Suzuki / Naoshi Dohmae / Mikako Shirouzu / Takashi Umehara / Abstract: 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8ham.cif.gz | 405.2 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8ham.ent.gz | 308 KB | Display | PDB format |
PDBx/mmJSON format | 8ham.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ha/8ham ftp://data.pdbj.org/pub/pdb/validation_reports/ha/8ham | HTTPS FTP |
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-Related structure data
Related structure data | 34596MC 8hagC 8hahC 8haiC 8hajC 8hakC 8halC 8hanC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 5 types, 9 molecules AEBFCGDHK
#1: Protein | Mass: 15305.969 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) Gene: 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, ...Gene: 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 Production host: Escherichia coli (E. coli) / References: UniProt: P68431 #2: Protein | Mass: 11345.289 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) #3: Protein | Mass: 14034.355 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H2AC4, H2AFM, HIST1H2AB, H2AC8, H2AFA, HIST1H2AE / Production host: Escherichia coli (E. coli) / References: UniProt: P04908 #4: Protein | Mass: 13804.045 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: H2BC11, H2BFR, HIST1H2BJ / Production host: Escherichia coli (E. coli) / References: UniProt: P06899 #6: Protein | | Mass: 92690.906 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CREBBP, CBP / Production host: Trichoplusia ni (cabbage looper) References: UniProt: Q92793, histone acetyltransferase, Transferases; Acyltransferases; Transferring groups other than aminoacyl groups |
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-DNA chain , 1 types, 2 molecules IJ
#5: DNA chain | Mass: 55560.527 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: the CBP catalytic core bound to the H4K12acK16ac nucleosome Type: COMPLEX / Details: CBP was expressed in insect cells. / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli (E. coli) |
Buffer solution | pH: 7.2 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1700 nm / Nominal defocus min: 900 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 90318 / Symmetry type: POINT | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 256.28 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
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