[English] 日本語
Yorodumi
- PDB-6g0q: Crystal Structure of the first bromodomain of human BRD4 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6g0q
TitleCrystal Structure of the first bromodomain of human BRD4 in complex with an acetylated GATA1 peptide (K312ac/K315ac)
Components
  • Bromodomain-containing protein 4
  • Erythroid transcription factor
KeywordsTRANSCRIPTION / Bromodomain / complex
Function / homology
Function and homology information


negative regulation of transcription regulatory region DNA binding / regulation of primitive erythrocyte differentiation / basophil differentiation / eosinophil fate commitment / regulation of definitive erythrocyte differentiation / eosinophil differentiation / regulation of glycoprotein biosynthetic process / primitive erythrocyte differentiation / myeloid cell apoptotic process / megakaryocyte differentiation ...negative regulation of transcription regulatory region DNA binding / regulation of primitive erythrocyte differentiation / basophil differentiation / eosinophil fate commitment / regulation of definitive erythrocyte differentiation / eosinophil differentiation / regulation of glycoprotein biosynthetic process / primitive erythrocyte differentiation / myeloid cell apoptotic process / megakaryocyte differentiation / osteoblast proliferation / Sertoli cell development / dendritic cell differentiation / negative regulation of bone mineralization / cellular response to follicle-stimulating hormone stimulus / positive regulation of mast cell degranulation / negative regulation of myeloid cell apoptotic process / C2H2 zinc finger domain binding / platelet formation / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of osteoblast proliferation / erythrocyte development / bone mineralization / RNA polymerase II C-terminal domain binding / P-TEFb complex binding / negative regulation of DNA damage checkpoint / histone H4 reader activity / host-mediated suppression of viral transcription / animal organ regeneration / positive regulation of G2/M transition of mitotic cell cycle / cell fate commitment / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of T-helper 17 cell lineage commitment / : / transcription repressor complex / RNA polymerase II CTD heptapeptide repeat kinase activity / homeostasis of number of cells within a tissue / positive regulation of erythrocyte differentiation / cellular response to cAMP / erythrocyte differentiation / condensed nuclear chromosome / transcription coregulator binding / transcription coregulator activity / RNA polymerase II transcription regulatory region sequence-specific DNA binding / positive regulation of transcription elongation by RNA polymerase II / protein-DNA complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / chromatin DNA binding / platelet aggregation / transcription coactivator binding / male gonad development / sequence-specific double-stranded DNA binding / p53 binding / cell-cell signaling / chromosome / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / cellular response to lipopolysaccharide / positive regulation of cytosolic calcium ion concentration / regulation of inflammatory response / DNA-binding transcription activator activity, RNA polymerase II-specific / histone binding / transcription regulator complex / in utero embryonic development / sequence-specific DNA binding / Potential therapeutics for SARS / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / DNA-binding transcription factor activity, RNA polymerase II-specific / transcription coactivator activity / positive regulation of canonical NF-kappaB signal transduction / transcription cis-regulatory region binding / RNA polymerase II cis-regulatory region sequence-specific DNA binding / chromatin remodeling / DNA-binding transcription factor activity / negative regulation of cell population proliferation / protein serine/threonine kinase activity / DNA damage response / chromatin binding / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / chromatin / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / DNA binding / zinc ion binding / nucleoplasm / nucleus
Similarity search - Function
Transcription factor GATA / GATA-type zinc finger domain. / GATA-type zinc finger domain profile. / zinc finger binding to DNA consensus sequence [AT]GATA[AG] / GATA zinc finger / Zinc finger, GATA-type / Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II ...Transcription factor GATA / GATA-type zinc finger domain. / GATA-type zinc finger domain profile. / zinc finger binding to DNA consensus sequence [AT]GATA[AG] / GATA zinc finger / Zinc finger, GATA-type / Bromodomain protein 4, C-terminal / C-terminal domain of bromodomain protein 4 / Brdt, bromodomain, repeat I / Brdt, bromodomain, repeat II / NET domain superfamily / NET domain profile. / : / NET domain / Bromodomain extra-terminal - transcription regulation / Bromodomain-like / Histone Acetyltransferase; Chain A / Zinc finger, NHR/GATA-type / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Up-down Bundle / Mainly Alpha
Similarity search - Domain/homology
Bromodomain-containing protein 4 / Erythroid transcription factor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.4 Å
AuthorsFilippakopoulos, P. / Picaud, S. / Newman, J. / Sorrell, F. / von Delft, F. / Arrowsmith, C.H. / Edwards, A.M. / Bountra, C.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Wellcome Trust095751/Z/11/Z United Kingdom
CitationJournal: Mol Cell / Year: 2019
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
DepositionMar 19, 2018Deposition site: PDBE / Processing site: PDBE
Revision 1.0Nov 28, 2018Provider: repository / Type: Initial release
Revision 1.1Dec 26, 2018Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Feb 20, 2019Group: Data collection / Database references
Category: citation / database_PDB_rev ...citation / database_PDB_rev / database_PDB_rev_record / pdbx_database_proc
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year
Revision 1.3Jan 17, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession
Revision 1.4Nov 13, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Bromodomain-containing protein 4
B: Erythroid transcription factor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)16,4283
Polymers16,3662
Non-polymers621
Water4,216234
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1380 Å2
ΔGint-5 kcal/mol
Surface area8400 Å2
MethodPISA
Unit cell
Length a, b, c (Å)39.284, 43.855, 82.344
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Bromodomain-containing protein 4 / Protein HUNK1


Mass: 15099.380 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BRD4, HUNK1 / Plasmid: pNIC28-Bsa4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): R3 / References: UniProt: O60885
#2: Protein/peptide Erythroid transcription factor / Eryf1 / GATA-binding factor 1 / GF-1 / NF-E1 DNA-binding protein


Mass: 1266.471 Da / Num. of mol.: 1 / Source method: obtained synthetically
Details: GATA1 peptide acetylated at K312 and K315 C-terminal TYR added for UV detection
Source: (synth.) Homo sapiens (human) / References: UniProt: P15976
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 234 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.21 Å3/Da / Density % sol: 44.24 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8 / Details: 30.0% PEG 1k 0.1M SPG pH 8.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: Apr 16, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.4→43.855 Å / Num. all: 28201 / Num. obs: 28201 / % possible obs: 98.4 % / Redundancy: 6.4 % / Rpim(I) all: 0.03 / Rrim(I) all: 0.078 / Rsym value: 0.071 / Net I/av σ(I): 5.7 / Net I/σ(I): 24.4 / Num. measured all: 179422
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. unique obsRpim(I) allRrim(I) allRsym value% possible all
1.4-1.486.40.0639.539980.0270.0690.06397.3
1.48-1.576.20.0619.738070.0260.0660.06197.6
1.57-1.676.60.0619.535940.0250.0670.06198.1
1.67-1.816.50.069.433700.0250.0650.0698.5
1.81-1.986.20.0591031290.0250.0640.05998.6
1.98-2.216.70.062928600.0260.0670.06299.2
2.21-2.566.30.0648.825390.0270.070.06499.4
2.56-3.136.20.0718.121840.0310.0780.07199.2
3.13-4.436.30.0847.717190.0360.0920.08499.4
4.43-43.8555.60.1046.110010.0470.1150.10498.6

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation2 Å43.85 Å
Translation2 Å43.85 Å

-
Processing

Software
NameVersionClassification
SCALA3.3.22data scaling
PHASER2.5.7phasing
REFMACrefinement
PDB_EXTRACT3.24data extraction
XDSdata reduction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: Ensemble of 2OSS, 2OUO, 2GRC, 2OO1, 3DAI, 3D7C, 3DWY

2oss

2ouo

2grc

2oo1

3dai

3d7c

3dwy


Resolution: 1.4→41.17 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.923 / SU B: 1.231 / SU ML: 0.023 / SU R Cruickshank DPI: 0.0625 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.063 / ESU R Free: 0.058
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.1784 1384 4.9 %RANDOM
Rwork0.1413 ---
obs0.1431 26788 97.97 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 75.43 Å2 / Biso mean: 9.027 Å2 / Biso min: 2.14 Å2
Baniso -1Baniso -2Baniso -3
1-0.11 Å20 Å20 Å2
2--0.04 Å2-0 Å2
3----0.15 Å2
Refinement stepCycle: final / Resolution: 1.4→41.17 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1131 0 4 234 1369
Biso mean--17.97 20.05 -
Num. residues----135
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0140.021169
X-RAY DIFFRACTIONr_bond_other_d0.0020.021132
X-RAY DIFFRACTIONr_angle_refined_deg1.6621.9891581
X-RAY DIFFRACTIONr_angle_other_deg0.98232619
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.275133
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.68225.53656
X-RAY DIFFRACTIONr_dihedral_angle_3_deg12.50215209
X-RAY DIFFRACTIONr_dihedral_angle_4_deg18.346154
X-RAY DIFFRACTIONr_chiral_restr0.1050.2164
X-RAY DIFFRACTIONr_gen_planes_refined0.0110.0211300
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02262
X-RAY DIFFRACTIONr_rigid_bond_restr2.6532301
X-RAY DIFFRACTIONr_sphericity_free21.087545
X-RAY DIFFRACTIONr_sphericity_bonded5.45552461
LS refinement shellResolution: 1.4→1.436 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.159 100 -
Rwork0.101 1918 -
all-2018 -
obs--96.69 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more