PDB-2kje: NMR structure of CBP TAZ2 and adenoviral E1A complex

Basic information

• Entry: Database: PDB / ID: 2kje
• Title: NMR structure of CBP TAZ2 and adenoviral E1A complex

Components

• CREB-binding protein
• Early E1A 32 kDa protein

• Keywords: TRANSCRIPTION / CBP / TAZ2 / E1A / adenoviral / Acetylation / Activator / Bromodomain / Chromosomal rearrangement / Disease mutation / Host-virus interaction / Isopeptide bond / Metal-binding / Methylation / Nucleus / Phosphoprotein / Transcription regulation / Transferase / Ubl conjugation / Zinc / Zinc-finger / Alternative splicing / DNA-binding / Early protein / Oncogene

Function / homology

Function:

regulation by virus of viral protein levels in host cell / Phosphorylation of CLOCK, acetylation of BMAL1 (ARNTL) at target gene promoters / The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex / positive regulation of protein sumoylation / peptide lactyltransferase (CoA-dependent) activity / NFE2L2 regulating ER-stress associated genes / NFE2L2 regulating inflammation associated genes / Activation of the TFAP2 (AP-2) family of transcription factors / histone H3K18 acetyltransferase activity / N-terminal peptidyl-lysine acetylation / histone H3K27 acetyltransferase activity / NFE2L2 regulates pentose phosphate pathway genes / LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production / regulation of smoothened signaling pathway / NFE2L2 regulating MDR associated enzymes / MRF binding / Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes / 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 / NOTCH4 Intracellular Domain Regulates Transcription / Regulation of NFE2L2 gene expression / Nuclear events mediated by NFE2L2 / Regulation of gene expression by Hypoxia-inducible Factor / negative regulation of transcription by RNA polymerase I / NOTCH3 Intracellular Domain Regulates Transcription / TRAF6 mediated IRF7 activation / NFE2L2 regulating tumorigenic genes / NFE2L2 regulating anti-oxidant/detoxification enzymes / embryonic digit morphogenesis / protein acetylation / Notch-HLH transcription pathway / Formation of paraxial mesoderm / acetyltransferase activity / positive regulation of transforming growth factor beta receptor signaling pathway / FOXO-mediated transcription of cell death genes / stimulatory C-type lectin receptor signaling pathway / homeostatic process / Zygotic genome activation (ZGA) / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / symbiont-mediated perturbation of host cell cycle G1/S transition checkpoint / histone acetyltransferase activity / molecular sequestering activity / histone acetyltransferase complex / protein-lysine-acetyltransferase activity / canonical NF-kappaB signal transduction / cAMP/PKA signal transduction / Attenuation phase / RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression / Expression of BMAL (ARNTL), CLOCK, and NPAS2 / histone acetyltransferase / regulation of cellular response to heat / positive regulation of double-strand break repair via homologous recombination / Regulation of lipid metabolism by PPARalpha / NPAS4 regulates expression of target genes / symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity / cellular response to nutrient levels / Transcriptional and post-translational regulation of MITF-M expression and activity / CD209 (DC-SIGN) signaling / BMAL1:CLOCK,NPAS2 activates circadian expression / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / SUMOylation of transcription cofactors / Activation of gene expression by SREBF (SREBP) / Heme signaling / PPARA activates gene expression / Transcriptional activation of mitochondrial biogenesis / Cytoprotection by HMOX1 / Formation of the beta-catenin:TCF transactivating complex / chromatin DNA binding / Transcriptional regulation of white adipocyte differentiation / positive regulation of protein localization to nucleus / Evasion by RSV of host interferon responses / NOTCH1 Intracellular Domain Regulates Transcription / Pre-NOTCH Transcription and Translation / protein destabilization / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / tau protein binding / transcription coactivator binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / p53 binding / cellular response to UV / transcription corepressor activity / rhythmic process / regulation of protein localization / HATs acetylate histones / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / protein-containing complex assembly / TRAF3-dependent IRF activation pathway / transcription regulator complex / Estrogen-dependent gene expression / DNA-binding transcription factor binding / molecular adaptor activity / damaged DNA binding / RNA polymerase II-specific DNA-binding transcription factor binding / symbiont-mediated perturbation of host ubiquitin-like protein modification / response to hypoxia / transcription coactivator activity / symbiont-mediated suppression of host innate immune response

Domain/homology:

Adenovirus early E1A protein / Early E1A protein / CREB-binding Protein; Chain A / TAZ domain / 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 / : / Histone acetyltransferase p300-like, PHD domain / 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. / Histone acetyltransferase Rtt109/CBP / Histone acetylation protein / Histone acetylation protein / Coactivator CBP, KIX domain superfamily / Zinc finger ZZ-type signature. / Zinc finger, ZZ type / Zinc-binding domain, present in Dystrophin, CREB-binding protein. / Zinc finger, ZZ-type / Zinc finger, ZZ-type superfamily / Zinc finger ZZ-type profile. / Nuclear receptor coactivator, interlocking / Bromodomain, conserved site / Bromodomain signature. / Bromodomain / bromo domain / Bromodomain / Bromodomain (BrD) profile. / Bromodomain-like superfamily / Zinc finger, RING/FYVE/PHD-type / Up-down Bundle / Mainly Alpha

Component:

Early E1A protein / CREB-binding protein

• Biological species: Homo sapiens (human); Human adenovirus 5
• Method: SOLUTION NMR / molecular dynamics
• Model details: lowest energy, model 1
• Authors: Ferreon, J.C. / Martinez-Yamout, M. / Dyson, H. / Wright, P.E.
• Citation: Journal: Proc.Natl.Acad.Sci.USA / Year: 2009; Title: Structural basis for subversion of cellular control mechanisms by the adenoviral E1A oncoprotein.; Authors: Ferreon, J.C. / Martinez-Yamout, M.A. / Dyson, H.J. / Wright, P.E.

History

Deposition	May 27, 2009	Deposition site: BMRB / Processing site: RCSB
Revision 1.0	Sep 15, 2009	Provider: repository / Type: Initial release
Revision 1.1	Jul 13, 2011	Group: Version format compliance
Revision 1.2	Mar 16, 2022	Group: Data collection / Database references / Derived calculations Category: database_2 / pdbx_nmr_software / pdbx_nmr_spectrometer / pdbx_struct_assembly / pdbx_struct_oper_list / struct_conn / struct_ref_seq_dif / struct_site Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_nmr_software.name / _pdbx_nmr_spectrometer.model / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.3	May 22, 2024	Group: Data collection / Category: chem_comp_atom / chem_comp_bond

Assembly

Deposited unit

A: CREB-binding protein

B: Early E1A 32 kDa protein

hetero molecules

Summary:

• 15.2 kDa, 2 polymers

Component details:

	Theoretical mass	Number of molelcules
Total (without water)	15,189	5
Polymers	14,992	2
Non-polymers	196	3
Water	0	0

1

Summary:

• Idetical with deposited unit
• defined by author

Symmetry operations:

Type	Name	Symmetry operation	Number
identity operation	1_555	x,y,z	1

NMR ensembles

	Data	Criteria
Number of conformers (submitted / calculated)	20 / 200	structures with the lowest energy
Representative	Model #1	lowest energy

Components

#1: Protein

A CREB-binding protein

Details:

Mass: 10527.567 Da / Num. of mol.: 1 / Fragment: UNP residues 1763-1854
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CREBBP, CBP / Plasmid: pET21a / Production host: Escherichia coli (E. coli) / References: UniProt: Q92793, histone acetyltransferase

#2: Protein/peptide

B Early E1A 32 kDa protein

Details:

Mass: 4464.908 Da / Num. of mol.: 1 / Fragment: UNP residues 53-91
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Human adenovirus 5 / Plasmid: pET21a / Production host: Escherichia coli (E. coli) / References: UniProt: P03255

#3: Chemical

A-500 A-501 A-502 ChemComp-ZN / ZINC ION

Details:

Mass: 65.409 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Zn

Experimental details

Experiment

• Experiment: Method: SOLUTION NMR

NMR experiment

Conditions-ID	Experiment-ID	Solution-ID	Type
1	1	1	2D 1H-15N HSQC
1	2	1	3D HNCA

Sample preparation

• Details: Contents: 1-1.5 mM [U-100% 13C; U-100% 15N] TRIS-1, 1-1.5 mM [U-100% 15N] TRIS-2, 100% D2O; Solvent system: 100% D2O

Sample

Units	Component	Isotopic labeling	Conc. range (mg/ml)	Solution-ID
mM	TRIS-1	[U-100% 13C; U-100% 15N]	1-1.5	1
mM	TRIS-2	[U-100% 15N]	1-1.5	1

• Sample conditions: Ionic strength: 0 / pH: 6.8 / Pressure: ambient / Temperature: 298 K

NMR measurement

NMR spectrometer

Type	Manufacturer	Model	Field strength (MHz)	Spectrometer-ID
Bruker DRX	Bruker	DRX	600	1
Bruker DRX	Bruker	DRX	800	2
Bruker Avance	Bruker	AVANCE	900	3

Processing

NMR software

Name	Developer	Classification
Amber	Case, Darden, Cheatham, III, Simmerling, Wang, Duke, Luo, ... and Kollm	data analysis
Amber	Case, Darden, Cheatham, III, Simmerling, Wang, Duke, Luo, ... and Kollm	refinement

• Refinement: Method: molecular dynamics / Software ordinal: 1
• NMR representative: Selection criteria: lowest energy
• NMR ensemble: Conformer selection criteria: structures with the lowest energy; Conformers calculated total number: 200 / Conformers submitted total number: 20