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- PDB-5nnc: Crystal Structure of the first bromodomain of human BRD4 in compl... -
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Open data
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Basic information
Entry | Database: PDB / ID: 5nnc | ||||||
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Title | Crystal Structure of the first bromodomain of human BRD4 in complex with a diacetylated histone 4 peptide (H3K9ac/K14ac) | ||||||
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![]() | TRANSCRIPTION / Bromodomain / complex | ||||||
Function / homology | ![]() RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / Chromatin modifying enzymes / positive regulation of T-helper 17 cell lineage commitment / epigenetic regulation of gene expression / positive regulation of G2/M transition of mitotic cell cycle / telomere organization / histone reader activity ...RNA polymerase II C-terminal domain binding / negative regulation of DNA damage checkpoint / P-TEFb complex binding / negative regulation by host of viral transcription / Chromatin modifying enzymes / positive regulation of T-helper 17 cell lineage commitment / epigenetic regulation of gene expression / positive regulation of G2/M transition of mitotic cell cycle / telomere organization / histone reader activity / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / RNA polymerase II CTD heptapeptide repeat kinase activity / DNA methylation / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / PRC2 methylates histones and DNA / condensed nuclear chromosome / Defective pyroptosis / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / positive regulation of transcription elongation by RNA polymerase II / Transcriptional regulation by small RNAs / transcription coregulator activity / Formation of the beta-catenin:TCF transactivating complex / lysine-acetylated histone binding / 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 / B-WICH complex positively regulates rRNA expression / HDMs demethylate histones / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / nucleosome / nucleosome assembly / p53 binding / chromatin organization / chromosome / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / gene expression / regulation of inflammatory response / Senescence-Associated Secretory Phenotype (SASP) / Oxidative Stress Induced Senescence / positive regulation of canonical NF-kappaB signal transduction / Estrogen-dependent gene expression / Potential therapeutics for SARS / transcription coactivator activity / transcription cis-regulatory region binding / chromatin remodeling / cadherin binding / protein heterodimerization activity / Amyloid fiber formation / DNA damage response / chromatin binding / chromatin / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / enzyme binding / positive regulation of transcription by RNA polymerase II / protein-containing complex / DNA binding / extracellular exosome / extracellular region / nucleoplasm / membrane / nucleus Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Filippakopoulos, P. / Picaud, S. / Pike, A.C.W. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C. | ||||||
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![]() | ![]() Title: Interactome Rewiring Following Pharmacological Targeting of BET Bromodomains. Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R ...Authors: Jean-Philippe Lambert / Sarah Picaud / Takao Fujisawa / Huayun Hou / Pavel Savitsky / Liis Uusküla-Reimand / Gagan D Gupta / Hala Abdouni / Zhen-Yuan Lin / Monika Tucholska / James D R Knight / Beatriz Gonzalez-Badillo / Nicole St-Denis / Joseph A Newman / Manuel Stucki / Laurence Pelletier / Nuno Bandeira / Michael D Wilson / Panagis Filippakopoulos / Anne-Claude Gingras / ![]() ![]() ![]() ![]() ![]() Abstract: Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, ...Targeting bromodomains (BRDs) of the bromo-and-extra-terminal (BET) family offers opportunities for therapeutic intervention in cancer and other diseases. Here, we profile the interactomes of BRD2, BRD3, BRD4, and BRDT following treatment with the pan-BET BRD inhibitor JQ1, revealing broad rewiring of the interaction landscape, with three distinct classes of behavior for the 603 unique interactors identified. A group of proteins associate in a JQ1-sensitive manner with BET BRDs through canonical and new binding modes, while two classes of extra-terminal (ET)-domain binding motifs mediate acetylation-independent interactions. Last, we identify an unexpected increase in several interactions following JQ1 treatment that define negative functions for BRD3 in the regulation of rRNA synthesis and potentially RNAPII-dependent gene expression that result in decreased cell proliferation. Together, our data highlight the contributions of BET protein modules to their interactomes allowing for a better understanding of pharmacological rewiring in response to JQ1. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 120.1 KB | Display | ![]() |
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PDB format | ![]() | 92.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 451.7 KB | Display | ![]() |
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Full document | ![]() | 452.8 KB | Display | |
Data in XML | ![]() | 12.5 KB | Display | |
Data in CIF | ![]() | 16.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 5nndC ![]() 5nneC ![]() 5nnfC ![]() 5nngC ![]() 6g0oC ![]() 6g0pC ![]() 6g0qC ![]() 6g0rC ![]() 6g0sC ![]() 2ossS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Unit cell |
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Components
#1: Protein | Mass: 15099.380 Da / Num. of mol.: 2 / Fragment: UNP residues 44-168 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein/peptide | Mass: 1993.271 Da / Num. of mol.: 2 / Fragment: UNP residues 5-21 / Source method: obtained synthetically / Details: Histone H3 peptide / Source: (synth.) ![]() #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 2.17 Å3/Da / Density % sol: 43.37 % |
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Crystal grow | Temperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 Details: 0.20M LiCl 0.1M TRIS pH 8.0 20.0% PEG 6K 10.0% EtGly |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 23, 2012 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 0.9686 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.205→19.86 Å / Num. obs: 13530 / % possible obs: 98.8 % / Redundancy: 3 % / Rmerge(I) obs: 0.061 / Rpim(I) all: 0.042 / Rrim(I) all: 0.074 / Rsym value: 0.061 / Net I/av σ(I): 7.5 / Net I/σ(I): 9.9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() | |||||||||
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Phasing MR | Model details: Phaser MODE: MR_AUTO
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 2OSS Resolution: 2.22→19.86 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.921 / SU B: 15.544 / SU ML: 0.194 / SU R Cruickshank DPI: 0.3207 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.321 / ESU R Free: 0.251 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES: WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 168.51 Å2 / Biso mean: 40.28 Å2 / Biso min: 17.96 Å2
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Refinement step | Cycle: final / Resolution: 2.22→19.86 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.215→2.272 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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