+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-11838 | ||||||||||||
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Title | Structure of the core MTA1/HDAC1/MBD2 NURD deacetylase complex | ||||||||||||
Map data | Core NuRD deacetylase complex | ||||||||||||
Sample |
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Keywords | Deacetylase / Complex / TRANSCRIPTION | ||||||||||||
Function / homology | Function and homology information Loss of MECP2 binding ability to 5mC-DNA / Krueppel-associated box domain binding / Repression of WNT target genes / MECP2 regulates transcription of neuronal ligands / satellite DNA binding / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / histone decrotonylase activity / ventricular cardiac muscle tissue development / fungiform papilla formation ...Loss of MECP2 binding ability to 5mC-DNA / Krueppel-associated box domain binding / Repression of WNT target genes / MECP2 regulates transcription of neuronal ligands / satellite DNA binding / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / histone decrotonylase activity / ventricular cardiac muscle tissue development / fungiform papilla formation / negative regulation of androgen receptor signaling pathway / negative regulation by host of viral transcription / NuRD complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / eyelid development in camera-type eye / endoderm development / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / maternal behavior / siRNA binding / protein deacetylation / E-box binding / Regulation of MITF-M-dependent genes involved in apoptosis / Transcription of E2F targets under negative control by DREAM complex / STAT3 nuclear events downstream of ALK signaling / positive regulation of protein autoubiquitination / histone deacetylase / methyl-CpG binding / C2H2 zinc finger domain binding / G0 and Early G1 / DNA methylation-dependent heterochromatin formation / protein lysine deacetylase activity / positive regulation of signaling receptor activity / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / SUMOylation of chromatin organization proteins / embryonic digit morphogenesis / histone deacetylase activity / positive regulation of oligodendrocyte differentiation / response to ionizing radiation / negative regulation of gene expression, epigenetic / positive regulation of stem cell population maintenance / G1/S-Specific Transcription / cellular response to platelet-derived growth factor stimulus / Notch-HLH transcription pathway / Sin3-type complex / entrainment of circadian clock by photoperiod / oligodendrocyte differentiation / odontogenesis of dentin-containing tooth / locomotor rhythm / RNA Polymerase I Transcription Initiation / histone deacetylase complex / SUMOylation of transcription factors / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / hair follicle placode formation / Regulation of MECP2 expression and activity / cellular response to organic cyclic compound / NF-kappaB binding / positive regulation of Wnt signaling pathway / RNA polymerase II core promoter sequence-specific DNA binding / embryonic organ development / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / heterochromatin / Nuclear events stimulated by ALK signaling in cancer / negative regulation of intrinsic apoptotic signaling pathway / MECP2 regulates neuronal receptors and channels / core promoter sequence-specific DNA binding / response to mechanical stimulus / negative regulation of canonical NF-kappaB signal transduction / Regulation of TP53 Activity through Acetylation / Regulation of PTEN gene transcription / RNA Polymerase I Promoter Opening / transcription repressor complex / response to nutrient levels / positive regulation of smooth muscle cell proliferation / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / transcription corepressor binding / negative regulation of transforming growth factor beta receptor signaling pathway / negative regulation of cell migration / HDACs deacetylate histones / Deactivation of the beta-catenin transactivating complex / promoter-specific chromatin binding / hippocampus development / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Formation of the beta-catenin:TCF transactivating complex / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / circadian regulation of gene expression / NoRC negatively regulates rRNA expression / negative regulation of canonical Wnt signaling pathway / heterochromatin formation / neuron differentiation / p53 binding / NOTCH1 Intracellular Domain Regulates Transcription / Wnt signaling pathway / histone deacetylase binding / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / transcription corepressor activity / nuclear envelope Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.1 Å | ||||||||||||
Authors | Millard CJ / Fairall L | ||||||||||||
Funding support | United Kingdom, 3 items
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Citation | Journal: Nucleic Acids Res / Year: 2020 Title: The topology of chromatin-binding domains in the NuRD deacetylase complex. Authors: Christopher J Millard / Louise Fairall / Timothy J Ragan / Christos G Savva / John W R Schwabe / Abstract: Class I histone deacetylase complexes play essential roles in many nuclear processes. Whilst they contain a common catalytic subunit, they have diverse modes of action determined by associated ...Class I histone deacetylase complexes play essential roles in many nuclear processes. Whilst they contain a common catalytic subunit, they have diverse modes of action determined by associated factors in the distinct complexes. The deacetylase module from the NuRD complex contains three protein domains that control the recruitment of chromatin to the deacetylase enzyme, HDAC1/2. Using biochemical approaches and cryo-electron microscopy, we have determined how three chromatin-binding domains (MTA1-BAH, MBD2/3 and RBBP4/7) are assembled in relation to the core complex so as to facilitate interaction of the complex with the genome. We observe a striking arrangement of the BAH domains suggesting a potential mechanism for binding to di-nucleosomes. We also find that the WD40 domains from RBBP4 are linked to the core with surprising flexibility that is likely important for chromatin engagement. A single MBD2 protein binds asymmetrically to the dimerisation interface of the complex. This symmetry mismatch explains the stoichiometry of the complex. Finally, our structures suggest how the holo-NuRD might assemble on a di-nucleosome substrate. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_11838.map.gz | 4 MB | EMDB map data format | |
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Header (meta data) | emd-11838-v30.xml emd-11838.xml | 24.9 KB 24.9 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11838_fsc.xml | 8.3 KB | Display | FSC data file |
Images | emd_11838.png | 133.7 KB | ||
Masks | emd_11838_msk_1.map | 46.4 MB | Mask map | |
Filedesc metadata | emd-11838.cif.gz | 7.4 KB | ||
Others | emd_11838_half_map_1.map.gz emd_11838_half_map_2.map.gz | 35.9 MB 35.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11838 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11838 | HTTPS FTP |
-Validation report
Summary document | emd_11838_validation.pdf.gz | 689.4 KB | Display | EMDB validaton report |
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Full document | emd_11838_full_validation.pdf.gz | 688.9 KB | Display | |
Data in XML | emd_11838_validation.xml.gz | 13.8 KB | Display | |
Data in CIF | emd_11838_validation.cif.gz | 19.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11838 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-11838 | HTTPS FTP |
-Related structure data
Related structure data | 7ao9MC 7ao8C 7aoaC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_11838.map.gz / Format: CCP4 / Size: 46.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Core NuRD deacetylase complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_11838_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Core NuRD deacetylase complex - half1
File | emd_11838_half_map_1.map | ||||||||||||
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Annotation | Core NuRD deacetylase complex - half1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Core NuRD deacetylase complex - half2
File | emd_11838_half_map_2.map | ||||||||||||
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Annotation | Core NuRD deacetylase complex - half2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Core NuRD deacetylase complex containing two copies of MTA1 and H...
Entire | Name: Core NuRD deacetylase complex containing two copies of MTA1 and HDAC1 and a single copy of MBD2 |
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Components |
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-Supramolecule #1: Core NuRD deacetylase complex containing two copies of MTA1 and H...
Supramolecule | Name: Core NuRD deacetylase complex containing two copies of MTA1 and HDAC1 and a single copy of MBD2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 170 KDa |
-Macromolecule #1: Methyl-CpG-binding domain protein 2
Macromolecule | Name: Methyl-CpG-binding domain protein 2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 43.323625 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG RGRWKQAGRG GGVCGRGRGR GRGRGRGRG RGRGRGRPPS GGSGLGGDGG GCGGGGSGGG GAPRREPVPF PSGSAGPGPR GPRATESGKR MDCPALPPGW K KEEVIRKS ...String: MRAHPGGGRC CPEQEEGESA AGGSGAGGDS AIEQGGQGSA LAPSPVSGVR REGARGGGRG RGRWKQAGRG GGVCGRGRGR GRGRGRGRG RGRGRGRPPS GGSGLGGDGG GCGGGGSGGG GAPRREPVPF PSGSAGPGPR GPRATESGKR MDCPALPPGW K KEEVIRKS GLSAGKSDVY YFSPSGKKFR SKPQLARYLG NTVDLSSFDF RTGKMMPSKL QKNKQRLRND PLNQNKGKPD LN TTLPIRQ TASIFKQPVT KVTNHPSNKV KSDPQRMNEQ PRQLFWEKRL QGLSASDVTE QIIKTMELPK GLQGVGPGSN DET LLSAVA SALHTSSAPI TGQVSAAVEK NPAVWLNTSQ PLCKAFIVTD EDIRKQEERV QQVRKKLEEA LMADILSRAA DTEE MDIEM DSGDEA UniProtKB: Methyl-CpG-binding domain protein 2 |
-Macromolecule #2: Metastasis-associated protein MTA1
Macromolecule | Name: Metastasis-associated protein MTA1 / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 80.904312 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAANMYRVGD YVYFENSSSN PYLIRRIEEL NKTANGNVEA KVVCFYRRRD ISSTLIALAD KHATLSVCYK AGPGADNGEE GEIEEEMEN PEMVDLPEKL KHQLRHRELF LSRQLESLPA THIRGKCSVT LLNETESLKS YLEREDFFFY SLVYDPQQKT L LADKGEIR ...String: MAANMYRVGD YVYFENSSSN PYLIRRIEEL NKTANGNVEA KVVCFYRRRD ISSTLIALAD KHATLSVCYK AGPGADNGEE GEIEEEMEN PEMVDLPEKL KHQLRHRELF LSRQLESLPA THIRGKCSVT LLNETESLKS YLEREDFFFY SLVYDPQQKT L LADKGEIR VGNRYQADIT DLLKEGEEDG RDQSRLETQV WEAHNPLTDK QIDQFLVVAR SVGTFARALD CSSSVRQPSL HM SAAAASR DITLFHAMDT LHKNIYDISK AISALVPQGG PVLCRDEMEE WSASEANLFE EALEKYGKDF TDIQQDFLPW KSL TSIIEY YYMWKTTDRY VQQKRLKAAE AESKLKQVYI PNYNKPNPNQ ISVNNVKAGV VNGTGAPGQS PGAGRACESC YTTQ SYQWY SWGPPNMQCR LCASCWTYWK KYGGLKMPTR LDGERPGPNR SNMSPHGLPA RSSGSPKFAM KTRQAFYLHT TKLTR IARR LCREILRPWH AARHPYLPIN SAAIKAECTA RLPEASQSPL VLKQAVRKPL EAVLRYLETH PRPPKPDPVK SVSSVL SSL TPAKVAPVIN NGSPTILGKR SYEQHNGVDG NMKKRLLMPS RGLANHGQAR HMGPSRNLLL NGKSYPTKVR LIRGGSL PP VKRRRMNWID APDDVFYMAT EETRKIRKLL SSSETKRAAR RPYKPIALRQ SQALPPRPPP PAPVNDEPIV IED UniProtKB: Metastasis-associated protein MTA1 |
-Macromolecule #3: Histone deacetylase 1
Macromolecule | Name: Histone deacetylase 1 / type: protein_or_peptide / ID: 3 / Number of copies: 2 / Enantiomer: LEVO / EC number: histone deacetylase |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 55.178906 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MAQTQGTRRK VCYYYDGDVG NYYYGQGHPM KPHRIRMTHN LLLNYGLYRK MEIYRPHKAN AEEMTKYHSD DYIKFLRSIR PDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA SAVKLNKQQT DIAVNWAGGL HHAKKSEASG FCYVNDIVLA I LELLKYHQ ...String: MAQTQGTRRK VCYYYDGDVG NYYYGQGHPM KPHRIRMTHN LLLNYGLYRK MEIYRPHKAN AEEMTKYHSD DYIKFLRSIR PDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA SAVKLNKQQT DIAVNWAGGL HHAKKSEASG FCYVNDIVLA I LELLKYHQ RVLYIDIDIH HGDGVEEAFY TTDRVMTVSF HKYGEYFPGT GDLRDIGAGK GKYYAVNYPL RDGIDDESYE AI FKPVMSK VMEMFQPSAV VLQCGSDSLS GDRLGCFNLT IKGHAKCVEF VKSFNLPMLM LGGGGYTIRN VARCWTYETA VAL DTEIPN ELPYNDYFEY FGPDFKLHIS PSNMTNQNTN EYLEKIKQRL FENLRMLPHA PGVQMQAIPE DAIPEESGDE DEDD PDKRI SICSSDKRIA CEEEFSDSEE EGEGGRKNSS NFKKAKRVKT EDEKEKDPEE KKEVTEEEKT KEEKPEAKGV KEEVK LA UniProtKB: Histone deacetylase 1 |
-Macromolecule #4: INOSITOL HEXAKISPHOSPHATE
Macromolecule | Name: INOSITOL HEXAKISPHOSPHATE / type: ligand / ID: 4 / Number of copies: 2 / Formula: IHP |
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Molecular weight | Theoretical: 660.035 Da |
Chemical component information | ChemComp-IHP: |
-Macromolecule #5: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 5 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #6: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 6 / Number of copies: 4 / Formula: K |
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Molecular weight | Theoretical: 39.098 Da |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.1 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GRAPHENE OXIDE / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Details: 40 mA for 120 sec | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV / Details: Blot for 3 seconds, blot force 10. |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Temperature | Min: 100.0 K |
Specialist optics | Phase plate: VOLTA PHASE PLATE |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 2 / Number real images: 3075 / Average exposure time: 60.0 sec. / Average electron dose: 34.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus min: 0.5 µm / Calibrated magnification: 129629 / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus min: 0.5 µm / Nominal magnification: 75000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |