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Basic information

Entry
Database: PDB / ID: 2agh
TitleStructural basis for cooperative transcription factor binding to the CBP coactivator
Components
  • Crebbp protein
  • Myb proto-oncogene protein
  • Zinc finger protein HRX
KeywordsTRANSCRIPTION
Function / homology
Function and homology information


positive regulation of testosterone secretion / Activation of the TFAP2 (AP-2) family of transcription factors / myeloid cell development / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / positive regulation of hepatic stellate cell proliferation / Attenuation phase / Regulation of gene expression by Hypoxia-inducible Factor / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production ...positive regulation of testosterone secretion / Activation of the TFAP2 (AP-2) family of transcription factors / myeloid cell development / Regulation of FOXO transcriptional activity by acetylation / TRAF6 mediated IRF7 activation / Nuclear events mediated by NFE2L2 / positive regulation of hepatic stellate cell proliferation / Attenuation phase / Regulation of gene expression by Hypoxia-inducible Factor / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / RUNX1 regulates transcription of genes involved in differentiation of myeloid cells / cAMP response element binding protein binding / Formation of the beta-catenin:TCF transactivating complex / NOTCH1 Intracellular Domain Regulates Transcription / RUNX3 regulates NOTCH signaling / Notch-HLH transcription pathway / positive regulation of hepatic stellate cell activation / protein-cysteine methyltransferase activity / positive regulation of cell adhesion molecule production / germ-line stem cell population maintenance / positive regulation of transforming growth factor beta production / response to potassium ion / negative regulation of viral process / Regulation of lipid metabolism by PPARalpha / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / Cytoprotection by HMOX1 / embryonic digestive tract development / unmethylated CpG binding / stem cell division / CD209 (DC-SIGN) signaling / histone H3K4 trimethyltransferase activity / Estrogen-dependent gene expression / peptide lactyltransferase (CoA-dependent) activity / outer kinetochore / negative regulation of DNA methylation-dependent heterochromatin formation / myeloid cell differentiation / negative regulation of interferon-beta production / regulation of short-term neuronal synaptic plasticity / histone H3K18 acetyltransferase activity / cellular response to interleukin-6 / N-terminal peptidyl-lysine acetylation / T-helper 2 cell differentiation / histone H3K27 acetyltransferase activity / definitive hemopoiesis / MRF binding / histone H3K4 methyltransferase activity / peroxisome proliferator activated receptor binding / face morphogenesis / embryonic hemopoiesis / negative regulation of transcription by RNA polymerase I / exploration behavior / WD40-repeat domain binding / anterior/posterior pattern specification / histone methyltransferase complex / peptide-lysine-N-acetyltransferase activity / cellular response to hepatocyte growth factor stimulus / positive regulation of dendritic spine development / Formation of WDR5-containing histone-modifying complexes / SMAD binding / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / behavioral response to cocaine / acetyltransferase activity / MLL1 complex / TFIIB-class transcription factor binding / positive regulation of double-strand break repair via homologous recombination / homeostasis of number of cells / histone acetyltransferase complex / positive regulation of collagen biosynthetic process / positive regulation of G1/S transition of mitotic cell cycle / long-term memory / negative regulation of fibroblast proliferation / histone acetyltransferase activity / positive regulation of glial cell proliferation / homeostasis of number of cells within a tissue / histone acetyltransferase / spleen development / transcription initiation-coupled chromatin remodeling / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / cellular response to transforming growth factor beta stimulus / Transferases; Transferring one-carbon groups; Methyltransferases / B cell differentiation / post-embryonic development / thymus development / cellular response to leukemia inhibitory factor / RNA polymerase II transcription regulatory region sequence-specific DNA binding / positive regulation of smooth muscle cell proliferation / circadian regulation of gene expression / protein destabilization / lysine-acetylated histone binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / visual learning / protein modification process / chromatin DNA binding / PKMTs methylate histone lysines / cellular response to virus / PML body / transcription coactivator binding / positive regulation of DNA-binding transcription factor activity
Similarity search - Function
Coactivator CBP, KIX domain / Transcription regulator Wos2-domain / LMSTEN motif / C-myb, C-terminal / C-myb, C-terminal / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax ...Coactivator CBP, KIX domain / Transcription regulator Wos2-domain / LMSTEN motif / C-myb, C-terminal / C-myb, C-terminal / KMT2A, ePHD domain / KMT2A, PHD domain 1 / KMT2A, PHD domain 2 / KMT2A, PHD domain 3 / Methyltransferase, trithorax / : / FY-rich, N-terminal / F/Y-rich N-terminus / PHD-like zinc-binding domain / FYR domain FYRN motif profile. / "FY-rich" domain, N-terminal region / FY-rich, C-terminal / F/Y rich C-terminus / FYR domain FYRC motif profile. / "FY-rich" domain, C-terminal region / CXXC zinc finger domain / Zinc finger, CXXC-type / Zinc finger CXXC-type profile. / Cysteine-rich motif following a subset of SET domains / Myb-type HTH DNA-binding domain profile. / Nuclear receptor coactivator, CREB-bp-like, interlocking / Nuclear receptor coactivator, CREB-bp-like, interlocking domain superfamily / Creb binding / Zinc finger, TAZ-type / TAZ domain superfamily / TAZ zinc finger / Zinc finger TAZ-type profile. / TAZ zinc finger, present in p300 and CBP / Coactivator CBP, KIX domain / CREB-binding protein/p300, atypical RING domain / CBP/p300-type histone acetyltransferase domain / CBP/p300, atypical RING domain superfamily / KIX domain / CREB-binding protein/p300, atypical RING domain / KIX domain profile. / CBP/p300-type histone acetyltransferase (HAT) domain profile. / Post-SET domain / Post-SET domain profile. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Serum Albumin; Chain A, Domain 1 / Myb domain / Zinc finger ZZ-type signature. / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ type / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Myb-like DNA-binding domain / SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain / SET domain superfamily / SET domain / SANT SWI3, ADA2, N-CoR and TFIIIB'' DNA-binding domains / Extended PHD (ePHD) domain / Extended PHD (ePHD) domain profile. / SET domain profile. / SET domain / SANT/Myb domain / Nuclear receptor coactivator, interlocking / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Homeobox-like domain superfamily / Zinc finger, FYVE/PHD-type / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / Bromodomain profile. / bromo domain / Bromodomain / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Transcriptional activator Myb / Histone lysine acetyltransferase CREBBP / Histone-lysine N-methyltransferase 2A
Similarity search - Component
Biological speciesMus musculus (house mouse)
Homo sapiens (human)
MethodSOLUTION NMR / simulated annealing
AuthorsDe Guzman, R.N. / Goto, N.K. / Dyson, H.J. / Wright, P.E.
CitationJournal: J.Mol.Biol. / Year: 2006
Title: Structural Basis for Cooperative Transcription Factor Binding to the CBP Coactivator
Authors: De Guzman, R.N. / Goto, N.K. / Dyson, H.J. / Wright, P.E.
History
DepositionJul 26, 2005Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 22, 2005Provider: repository / Type: Initial release
Revision 1.1Apr 30, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Jul 7, 2021Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: diffrn / diffrn_radiation ...diffrn / diffrn_radiation / diffrn_radiation_wavelength / pdbx_nmr_ensemble / pdbx_nmr_refine / pdbx_nmr_software / pdbx_nmr_spectrometer / pdbx_struct_assembly / pdbx_struct_oper_list / struct_ref_seq_dif
Item: _pdbx_nmr_ensemble.conformer_selection_criteria / _pdbx_nmr_refine.method ..._pdbx_nmr_ensemble.conformer_selection_criteria / _pdbx_nmr_refine.method / _pdbx_nmr_spectrometer.manufacturer / _pdbx_nmr_spectrometer.model / _struct_ref_seq_dif.details
Revision 1.4May 1, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Myb proto-oncogene protein
B: Crebbp protein
C: Zinc finger protein HRX


Theoretical massNumber of molelcules
Total (without water)16,6113
Polymers16,6113
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 100lowest energy and lowest distance and angle violations
RepresentativeModel #1lowest energy

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Components

#1: Protein/peptide Myb proto-oncogene protein / C-myb


Mass: 2947.469 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Myb / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P06876
#2: Protein Crebbp protein


Mass: 10353.856 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: CBP, CREBBP / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: P45481
#3: Protein/peptide Zinc finger protein HRX / ALL-1 / Trithorax-like protein


Mass: 3309.611 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MLL, ALL1, HRX, HTRX, TRX1 / Plasmid: pET / Species (production host): Escherichia coli / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q03164

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1112D 15N HSQC
1212D 13C HSQC
1312D 13C-{13C} SED
1412D 13C-{15N} SED
1513D HNCA
1613D HN(CA)CB
1713D CBCA(CO)NH
1813D HBHA(CBCACO)NH
1913D C(CO)NH-TOCSY
11013D H(CCO)NH-TOCSY
11113D CCH-COSY
11213D CCH-TOCSY
11313D (H)CCH-TOCSY
11413D HACAHB-COSY
11513D HNHB
11613D HNHA
11713D 13C-EDITED NOESY
11813D 13C,15N-EDITED NOESY
11913D 12C-FILTERED/13C-EDITED NOESY

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Sample preparation

Details
Solution-IDContentsSolvent system
10.5-0.8 mM 15N,13C-labeled protein (e.g. CBP) + 3 fold excess of unlabeled binding partners (MYB + MLL), 20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O
213C,15N-MYB + UNLABELED CBP & MYB, 20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O
313C,15N-MLL + UNLABELED CBP & MLL, 20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O20 mM Tris-d3-acetate, 50 mM NaCl, 0.2% sodium azide, 10% D2O
Sample conditionspH: 5.5 / Pressure: 1 atm / Temperature: 298 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Bruker AVANCEBrukerAVANCE9001
Bruker AVANCEBrukerAVANCE8002
Bruker DRXBrukerDRX7503
Bruker DRXBrukerDRX6004

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Processing

NMR software
NameDeveloperClassification
AmberDavid Case et al.refinement
DYANAGuntert, Braun and Wuthrichstructure calculation
RefinementMethod: simulated annealing / Software ordinal: 1
Details: iNITIAL STRUCTURE CALCULATION USING TORSION ANGLE DYNAMICS IN DYANA FOLLOWED BY REFINEMENT IN AMBER USING SIMULATED ANNEALING AND ENERGY MINIMIZATION IN VACUO AND GENERALIZED BORN POTENTIAL
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: lowest energy and lowest distance and angle violations
Conformers calculated total number: 100 / Conformers submitted total number: 20

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