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Yorodumi- EMDB-26809: KDM2A-nucleosome structure stabilized by H3K36C-UNC8015 covalent ... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26809 | |||||||||||||||
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Title | KDM2A-nucleosome structure stabilized by H3K36C-UNC8015 covalent conjugate | |||||||||||||||
Map data | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate | |||||||||||||||
Sample |
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Keywords | chromatin nucleosome lysine demethylase JmjC protein / GENE REGULATION-DNA complex | |||||||||||||||
Function / homology | Function and homology information histone H3K36me/H3K36me2 demethylase activity / [histone H3]-dimethyl-L-lysine36 demethylase / unmethylated CpG binding / histone H3K36 demethylase activity / negative regulation of transcription by competitive promoter binding / histone demethylase activity / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends ...histone H3K36me/H3K36me2 demethylase activity / [histone H3]-dimethyl-L-lysine36 demethylase / unmethylated CpG binding / histone H3K36 demethylase activity / negative regulation of transcription by competitive promoter binding / histone demethylase activity / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / Packaging Of Telomere Ends / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / transcription coregulator activity / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / Interleukin-7 signaling / DNA methylation / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / regulation of circadian rhythm / Transcriptional regulation by small RNAs / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / circadian regulation of gene expression / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / double-strand break repair via nonhomologous end joining / structural constituent of chromatin / chromosome / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / E3 ubiquitin ligases ubiquitinate target proteins / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / antibacterial humoral response / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / regulation of transcription by RNA polymerase II / enzyme binding / DNA binding / extracellular space / zinc ion binding / extracellular exosome / extracellular region / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol Similarity search - Function | |||||||||||||||
Biological species | Homo sapiens (human) / synthetic construct (others) | |||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||||||||
Authors | Spangler CJ / Skrajna A / Foley CA / Budziszewski GR / Azzam DN / James LI / Frye SV / McGinty RK | |||||||||||||||
Funding support | United States, 4 items
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Citation | Journal: Nat Chem Biol / Year: 2023 Title: Structural basis of paralog-specific KDM2A/B nucleosome recognition. Authors: Cathy J Spangler / Aleksandra Skrajna / Caroline A Foley / Anh Nguyen / Gabrielle R Budziszewski / Dalal N Azzam / Eyla C Arteaga / Holly C Simmons / Charlotte B Smith / Nathaniel A Wesley / ...Authors: Cathy J Spangler / Aleksandra Skrajna / Caroline A Foley / Anh Nguyen / Gabrielle R Budziszewski / Dalal N Azzam / Eyla C Arteaga / Holly C Simmons / Charlotte B Smith / Nathaniel A Wesley / Emily M Wilkerson / Jeanne-Marie E McPherson / Dmitri Kireev / Lindsey I James / Stephen V Frye / Dennis Goldfarb / Robert K McGinty / Abstract: The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic ...The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. Despite fundamental roles in transcriptional repression in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any related JumonjiC (JmjC) domain lysine demethylase, remain unclear. We used a covalent conjugate between H3K36 and a demethylase inhibitor to solve cryogenic electron microscopy structures of KDM2A and KDM2B trapped in action on a nucleosome substrate. Our structures show that KDM2-nucleosome binding is paralog specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation. | |||||||||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_26809.map.gz | 9.5 MB | EMDB map data format | |
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Header (meta data) | emd-26809-v30.xml emd-26809.xml | 29.3 KB 29.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26809_fsc.xml | 11.6 KB | Display | FSC data file |
Images | emd_26809.png | 129.1 KB | ||
Filedesc metadata | emd-26809.cif.gz | 7.9 KB | ||
Others | emd_26809_additional_1.map.gz emd_26809_half_map_1.map.gz emd_26809_half_map_2.map.gz | 107.3 MB 42.1 MB 42.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26809 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26809 | HTTPS FTP |
-Validation report
Summary document | emd_26809_validation.pdf.gz | 564.1 KB | Display | EMDB validaton report |
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Full document | emd_26809_full_validation.pdf.gz | 563.6 KB | Display | |
Data in XML | emd_26809_validation.xml.gz | 18.5 KB | Display | |
Data in CIF | emd_26809_validation.cif.gz | 23.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26809 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26809 | HTTPS FTP |
-Related structure data
Related structure data | 7uv9MC 7uvaC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_26809.map.gz / Format: CCP4 / Size: 137.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.91 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate multibody...
File | emd_26809_additional_1.map | ||||||||||||
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Annotation | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate multibody refinement nucleosome mask | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half...
File | emd_26809_half_map_1.map | ||||||||||||
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Annotation | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half...
File | emd_26809_half_map_2.map | ||||||||||||
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Annotation | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half map 2 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent co...
+Supramolecule #1: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent co...
+Macromolecule #1: Histone H3.2
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1
+Macromolecule #4: Histone H2B type 1-C/E/F/G/I
+Macromolecule #7: Lysine-specific demethylase 2A
+Macromolecule #5: DNA (185-MER)
+Macromolecule #6: DNA (185-MER)
+Macromolecule #8: N-heptanoyl-N-hydroxy-beta-alanine
+Macromolecule #9: FE (III) ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 1 mg/mL | |||||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 60 sec. / Details: Tergeo EM plasma cleaner | |||||||||
Vitrification | Cryogen name: ETHANE-PROPANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 9075 / Average electron dose: 45.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm / Nominal magnification: 45000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | Model: Talos Arctica / Image courtesy: FEI Company |