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Yorodumi- EMDB-11839: Structure of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase ... -
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-Basic information
Entry | Database: EMDB / ID: EMD-11839 | ||||||||||||
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Title | Structure of the extended MTA1/HDAC1/MBD2/RBBP4 NURD deacetylase complex | ||||||||||||
Map data | Extended 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 / CAF-1 complex / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / ventricular cardiac muscle tissue development / histone decrotonylase activity ...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 / CAF-1 complex / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / ventricular cardiac muscle tissue development / histone decrotonylase activity / fungiform papilla formation / negative regulation of androgen receptor signaling pathway / NURF complex / regulation of amyloid-beta clearance / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / endoderm development / DNA methylation-dependent heterochromatin formation / NuRD complex / maternal behavior / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / ESC/E(Z) complex / protein deacetylation / siRNA binding / Transcription of E2F targets under negative control by DREAM complex / STAT3 nuclear events downstream of ALK signaling / Polo-like kinase mediated events / positive regulation of protein autoubiquitination / histone deacetylase / C2H2 zinc finger domain binding / methyl-CpG binding / protein lysine deacetylase activity / positive regulation of signaling receptor activity / regulation of endopeptidase activity / Hydrolases; Acting on carbon-nitrogen bonds, other than peptide bonds; In linear amides / histone deacetylase activity / embryonic digit morphogenesis / negative regulation of gene expression, epigenetic / positive regulation of oligodendrocyte differentiation / response to ionizing radiation / ATPase complex / positive regulation of stem cell population maintenance / Sin3-type complex / G1/S-Specific Transcription / cellular response to platelet-derived growth factor stimulus / Notch-HLH transcription pathway / eyelid development in camera-type eye / oligodendrocyte differentiation / E-box binding / Transcriptional Regulation by E2F6 / entrainment of circadian clock by photoperiod / locomotor rhythm / odontogenesis of dentin-containing tooth / RNA Polymerase I Transcription Initiation / histone deacetylase complex / SUMOylation of transcription factors / hair follicle placode formation / Regulation of MECP2 expression and activity / cellular response to organic cyclic compound / G0 and Early G1 / positive regulation of Wnt signaling pathway / NF-kappaB binding / negative regulation by host of viral transcription / RNA polymerase II core promoter sequence-specific DNA binding / embryonic organ development / heterochromatin / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of intrinsic apoptotic signaling pathway / Cyclin E associated events during G1/S transition / response to mechanical stimulus / negative regulation of canonical NF-kappaB signal transduction / core promoter sequence-specific DNA binding / MECP2 regulates neuronal receptors and channels / Cyclin A:Cdk2-associated events at S phase entry / Deposition of new CENPA-containing nucleosomes at the centromere / Regulation of TP53 Activity through Acetylation / transcription repressor complex / RNA Polymerase I Promoter Opening / SUMOylation of chromatin organization proteins / response to nutrient levels / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / Defective pyroptosis / Deactivation of the beta-catenin transactivating complex / HDACs deacetylate histones / promoter-specific chromatin binding / hippocampus development / Downregulation of SMAD2/3:SMAD4 transcriptional activity / SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription / positive regulation of smooth muscle cell proliferation / negative regulation of transforming growth factor beta receptor signaling pathway / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / brain development Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 19.4 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_11839.map.gz | 1.2 MB | EMDB map data format | |
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Header (meta data) | emd-11839-v30.xml emd-11839.xml | 26.7 KB 26.7 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_11839_fsc.xml | 6.5 KB | Display | FSC data file |
Images | emd_11839.png | 84.5 KB | ||
Masks | emd_11839_msk_1.map | 22.2 MB | Mask map | |
Filedesc metadata | emd-11839.cif.gz | 7.8 KB | ||
Others | emd_11839_half_map_1.map.gz emd_11839_half_map_2.map.gz | 17 MB 17 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-11839 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-11839 | HTTPS FTP |
-Related structure data
Related structure data | 7aoaMC 7ao8C 7ao9C 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_11839.map.gz / Format: CCP4 / Size: 22.2 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Extended NuRD deacetylase complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 2.16 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_11839_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Extended NuRD deacetylase complex - half1
File | emd_11839_half_map_1.map | ||||||||||||
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Annotation | Extended NuRD deacetylase complex - half1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Extended NuRD deacetylase complex - half2
File | emd_11839_half_map_2.map | ||||||||||||
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Annotation | Extended NuRD deacetylase complex - half2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Extended NuRD deacetylase complex containing two copies of MTA1, ...
Entire | Name: Extended NuRD deacetylase complex containing two copies of MTA1, HDAC1 and RBBP4 and a single copy of MBD2 |
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Components |
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-Supramolecule #1: Extended NuRD deacetylase complex containing two copies of MTA1, ...
Supramolecule | Name: Extended NuRD deacetylase complex containing two copies of MTA1, HDAC1 and RBBP4 and a single copy of MBD2 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#4 |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 340 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: Histone-binding protein RBBP4
Macromolecule | Name: Histone-binding protein RBBP4 / type: protein_or_peptide / ID: 4 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 47.709527 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN ...String: MADKEAAFDD AVEERVINEE YKIWKKNTPF LYDLVMTHAL EWPSLTAQWL PDVTRPEGKD FSIHRLVLGT HTSDEQNHLV IASVQLPND DAQFDASHYD SEKGEFGGFG SVSGKIEIEI KINHEGEVNR ARYMPQNPCI IATKTPSSDV LVFDYTKHPS K PDPSGECN PDLRLRGHQK EGYGLSWNPN LSGHLLSASD DHTICLWDIS AVPKEGKVVD AKTIFTGHTA VVEDVSWHLL HE SLFGSVA DDQKLMIWDT RSNNTSKPSH SVDAHTAEVN CLSFNPYSEF ILATGSADKT VALWDLRNLK LKLHSFESHK DEI FQVQWS PHNETILASS GTDRRLNVWD LSKIGEEQSP EDAEDGPPEL LFIHGGHTAK ISDFSWNPNE PWVICSVSED NIMQ VWQMA ENIYNDEDPE GSVDPEGQGS UniProtKB: Histone-binding protein RBBP4 |
-Macromolecule #5: INOSITOL HEXAKISPHOSPHATE
Macromolecule | Name: INOSITOL HEXAKISPHOSPHATE / type: ligand / ID: 5 / Number of copies: 2 / Formula: IHP |
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Molecular weight | Theoretical: 660.035 Da |
Chemical component information | ChemComp-IHP: |
-Macromolecule #6: ZINC ION
Macromolecule | Name: ZINC ION / type: ligand / ID: 6 / Number of copies: 2 / Formula: ZN |
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Molecular weight | Theoretical: 65.409 Da |
-Macromolecule #7: POTASSIUM ION
Macromolecule | Name: POTASSIUM ION / type: ligand / ID: 7 / 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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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 FIELDBright-field microscopy / Cs: 2.7 mm / Nominal defocus min: 0.5 µm / Nominal magnification: 75000 |
Specialist optics | Phase plate: VOLTA PHASE PLATE |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Temperature | Min: 100.0 K |
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: 1 / Number real images: 1902 / Average exposure time: 60.0 sec. / Average electron dose: 34.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
-Atomic model buiding 1
Initial model |
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Refinement | Protocol: RIGID BODY FIT | ||||||||
Output model | PDB-7aoa: |