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- PDB-6irr: Solution structure of DISC1/ATF4 complex -

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Basic information

Entry
Database: PDB / ID: 6irr
TitleSolution structure of DISC1/ATF4 complex
ComponentsDisrupted in schizophrenia 1 homolog,Cyclic AMP-dependent transcription factor ATF-4
KeywordsSTRUCTURAL PROTEIN / Scaffold protein / Psychiatric disorder / coiled coil
Function / homology
Function and homology information


L-asparagine metabolic process / ATF1-ATF4 transcription factor complex / CHOP-ATF4 complex / Lewy body core / pyramidal neuron migration to cerebral cortex / ATF4-CREB1 transcription factor complex / positive regulation of sodium-dependent phosphate transport / positive regulation of biomineral tissue development / leucine zipper domain binding / integrated stress response signaling ...L-asparagine metabolic process / ATF1-ATF4 transcription factor complex / CHOP-ATF4 complex / Lewy body core / pyramidal neuron migration to cerebral cortex / ATF4-CREB1 transcription factor complex / positive regulation of sodium-dependent phosphate transport / positive regulation of biomineral tissue development / leucine zipper domain binding / integrated stress response signaling / cAMP response element binding protein binding / HRI-mediated signaling / mitochondrial calcium ion homeostasis / response to manganese-induced endoplasmic reticulum stress / cell proliferation in forebrain / central region of growth cone / cerebral cortex radially oriented cell migration / PERK-mediated unfolded protein response / regulation of dendritic spine development / cellular response to leucine starvation / lens fiber cell morphogenesis / regulation of synapse maturation / non-motile cilium assembly / intermediate filament cytoskeleton / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / positive regulation of ubiquitin-dependent protein catabolic process / dynein complex / protein localization to centrosome / regulation of postsynapse organization / kinesin complex / negative regulation of cold-induced thermogenesis / embryonic hemopoiesis / positive regulation of vascular associated smooth muscle cell apoptotic process / positive regulation of cell-matrix adhesion / regulation of osteoblast differentiation / positive regulation of neuroblast proliferation / gamma-aminobutyric acid signaling pathway / ciliary base / bone mineralization / regulation of neuron projection development / positive regulation of transcription by RNA polymerase I / detection of temperature stimulus involved in sensory perception of pain / negative regulation of potassium ion transport / TOR signaling / positive regulation of vascular endothelial growth factor production / kinesin binding / general transcription initiation factor binding / response to electrical stimulus / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of Wnt signaling pathway / canonical Wnt signaling pathway / positive regulation of axon extension / endoplasmic reticulum unfolded protein response / cellular response to glucose starvation / regulation of synaptic transmission, glutamatergic / dendrite membrane / nuclear periphery / cellular response to amino acid starvation / response to endoplasmic reticulum stress / gluconeogenesis / RNA polymerase II transcription regulatory region sequence-specific DNA binding / mRNA transcription by RNA polymerase II / promoter-specific chromatin binding / circadian regulation of gene expression / GABA-ergic synapse / positive regulation of neuron projection development / regulation of synaptic plasticity / response to toxic substance / microtubule cytoskeleton organization / RNA polymerase II transcription regulator complex / circadian rhythm / neuron cellular homeostasis / intracellular calcium ion homeostasis / neuron migration / neuron differentiation / intracellular protein localization / synaptic vesicle / positive regulation of neuron apoptotic process / cell body / DNA-binding transcription activator activity, RNA polymerase II-specific / cellular response to oxidative stress / ubiquitin-dependent protein catabolic process / cellular response to hypoxia / molecular adaptor activity / transcription regulator complex / DNA-binding transcription factor binding / microtubule / RNA polymerase II-specific DNA-binding transcription factor binding / transcription by RNA polymerase II / postsynaptic density / nuclear speck / ciliary basal body / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein heterodimerization activity / centrosome / positive regulation of gene expression / regulation of transcription by RNA polymerase II / regulation of DNA-templated transcription / protein kinase binding
Similarity search - Function
Disrupted in schizophrenia 1 / bZIP transcription factor / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain / Basic-leucine zipper domain superfamily
Similarity search - Domain/homology
Cyclic AMP-dependent transcription factor ATF-4 / Disrupted in schizophrenia 1 homolog
Similarity search - Component
Biological speciesMus musculus (house mouse)
MethodSOLUTION NMR / simulated annealing
AuthorsYe, F. / Yu, C. / Zhang, M.
Funding support Hong Kong, 1items
OrganizationGrant numberCountry
16104518 Hong Kong
CitationJournal: Mol. Psychiatry / Year: 2019
Title: Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders.
Authors: Wang, X. / Ye, F. / Wen, Z. / Guo, Z. / Yu, C. / Huang, W.K. / Rojas Ringeling, F. / Su, Y. / Zheng, W. / Zhou, G. / Christian, K.M. / Song, H. / Zhang, M. / Ming, G.L.
History
DepositionNov 14, 2018Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Sep 25, 2019Provider: repository / Type: Initial release
Revision 1.1Jun 14, 2023Group: Database references / Other / Category: citation / database_2 / pdbx_database_status
Item: _citation.country / _database_2.pdbx_DOI ..._citation.country / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_nmr_data
Revision 1.2May 15, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2 / Item: _database_2.pdbx_DOI

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Disrupted in schizophrenia 1 homolog,Cyclic AMP-dependent transcription factor ATF-4


Theoretical massNumber of molelcules
Total (without water)14,5651
Polymers14,5651
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area0 Å2
ΔGint0 kcal/mol
Surface area12790 Å2
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 43structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein Disrupted in schizophrenia 1 homolog,Cyclic AMP-dependent transcription factor ATF-4 / cAMP-dependent transcription factor ATF-4 / Activating transcription factor 4 / C/EBP-related ATF / ...cAMP-dependent transcription factor ATF-4 / Activating transcription factor 4 / C/EBP-related ATF / C/ATF / Tax-responsive enhancer element-binding protein 67 homolog / TaxREB67 homolog


Mass: 14565.497 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Gene: Disc1, Atf4 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3) / References: UniProt: Q811T9, UniProt: Q06507
Sequence detailsSequence of the protein was based on Isoform 2 of database UNP Q811T9 (DISC1_MOUSE).

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDSample stateSpectrometer-IDType
112isotropic13D 1H-15N NOESY
121isotropic23D 1H-13C NOESY
133isotropic12D 1H-1H NOESY
141isotropic23D CBCA(CO)NH
151isotropic23D HN(CA)CB

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Sample preparation

Details
TypeSolution-IDContentsLabelSolvent system
solution10.8 mM [U-100% 13C; U-100% 15N] DISC1/ATF4 complex, 1 mM DTT, 1 mM EDTA, 100 mM potassium phosphate, 100% D2O15N, 13C100% D2O
solution20.8 mM [U-99% 15N] DISC1/ATF4 complex, 1 mM DTT, 1 mM EDTA, 100 mM potassium phosphate, 90% H2O/10% D2O15N90% H2O/10% D2O
solution30.8 mM DISC1/ATF4 complex, 1 mM DTT, 1 mM EDTA, 100 mM potassium phosphate, 100% D2Ounlabeled100% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.8 mMDISC1/ATF4 complex[U-100% 13C; U-100% 15N]1
1 mMDTTnatural abundance1
1 mMEDTAnatural abundance1
100 mMpotassium phosphatenatural abundance1
0.8 mMDISC1/ATF4 complex[U-99% 15N]2
1 mMDTTnatural abundance2
1 mMEDTAnatural abundance2
100 mMpotassium phosphatenatural abundance2
0.8 mMDISC1/ATF4 complexnatural abundance3
1 mMDTTnatural abundance3
1 mMEDTAnatural abundance3
100 mMpotassium phosphatenatural abundance3
Sample conditionsIonic strength: 100mM potassium phosphate Not defined / Label: conditions1 / pH: 6.5 / Pressure: ambient Pa / Temperature: 303 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Varian INOVAVarianINOVA7501
Varian INOVAVarianINOVA8002

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Processing

NMR software
NameDeveloperClassification
CNSBrunger A. T. et.al.refinement
CNSBrunger A. T. et.al.structure calculation
SparkyGoddardchemical shift assignment
PIPPGarrettpeak picking
RefinementMethod: simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 43 / Conformers submitted total number: 20

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