+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28915 | |||||||||
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Title | SIRT6 bound to an H3K9Ac nucleosome | |||||||||
Map data | map A | |||||||||
Sample |
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Keywords | nucleosome / SIRTUIN6 / histone deacylation / H3K9Ac / GENE REGULATION | |||||||||
Function / homology | Function and homology information histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / TORC2 complex binding / ketone biosynthetic process / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity ...histone H3K56 deacetylase activity, NAD-dependent / histone H3K18 deacetylase activity, NAD-dependent / histone H3K9 deacetylase activity, NAD-dependent / protein delipidation / TORC2 complex binding / ketone biosynthetic process / NAD+-protein-lysine ADP-ribosyltransferase activity / regulation of lipid catabolic process / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / chromosome, subtelomeric region / NAD+-protein-arginine ADP-ribosyltransferase activity / positive regulation of protein localization to chromatin / DNA damage sensor activity / positive regulation of stem cell differentiation / positive regulation of blood vessel branching / NAD-dependent protein lysine deacetylase activity / transposable element silencing / protein acetyllysine N-acetyltransferase / positive regulation of chondrocyte proliferation / cardiac muscle cell differentiation / positive regulation of telomere maintenance / histone deacetylase activity, NAD-dependent / pericentric heterochromatin formation / negative regulation of D-glucose import / protein deacetylation / protein localization to site of double-strand break / negative regulation of glycolytic process / lncRNA binding / positive regulation of double-strand break repair / negative regulation of protein localization to chromatin / DNA repair-dependent chromatin remodeling / positive regulation of vascular endothelial cell proliferation / negative regulation of protein import into nucleus / regulation of double-strand break repair via homologous recombination / negative regulation of gene expression, epigenetic / positive regulation of stem cell population maintenance / regulation of protein secretion / positive regulation of stem cell proliferation / negative regulation of transcription elongation by RNA polymerase II / NAD+-protein ADP-ribosyltransferase activity / negative regulation of cellular senescence / site of DNA damage / regulation of lipid metabolic process / NAD+-protein poly-ADP-ribosyltransferase activity / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ binding / subtelomeric heterochromatin formation / regulation of protein localization to plasma membrane / positive regulation of fat cell differentiation / nucleosome binding / negative regulation of gluconeogenesis / pericentric heterochromatin / response to UV / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / nucleotidyltransferase activity / positive regulation of protein export from nucleus / determination of adult lifespan / circadian regulation of gene expression / protein destabilization / base-excision repair / positive regulation of insulin secretion / regulation of circadian rhythm / chromatin DNA binding / Pre-NOTCH Transcription and Translation / structural constituent of chromatin / transcription corepressor activity / positive regulation of fibroblast proliferation / nucleosome / double-strand break repair / positive regulation of cold-induced thermogenesis / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / nucleosome assembly / glucose homeostasis / site of double-strand break / Processing of DNA double-strand break ends / damaged DNA binding / chromatin remodeling / protein heterodimerization activity / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / chromatin binding / chromatin / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / protein homodimerization activity / DNA binding / zinc ion binding / nucleoplasm / nucleus Similarity search - Function | |||||||||
Biological species | Xenopus laevis (African clawed frog) / Homo sapiens (human) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.1 Å | |||||||||
Authors | Markert J / Whedon S / Wang Z / Cole P / Farnung L | |||||||||
Funding support | 1 items
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Citation | Journal: J Am Chem Soc / Year: 2023 Title: Structural Basis of Sirtuin 6-Catalyzed Nucleosome Deacetylation. Authors: Zhipeng A Wang / Jonathan W Markert / Samuel D Whedon / Maheeshi Yapa Abeywardana / Kwangwoon Lee / Hanjie Jiang / Carolay Suarez / Hening Lin / Lucas Farnung / Philip A Cole / Abstract: The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins ...The reversible acetylation of histone lysine residues is controlled by the action of acetyltransferases and deacetylases (HDACs), which regulate chromatin structure and gene expression. The sirtuins are a family of NAD-dependent HDAC enzymes, and one member, sirtuin 6 (Sirt6), influences DNA repair, transcription, and aging. Here, we demonstrate that Sirt6 is efficient at deacetylating several histone H3 acetylation sites, including its canonical site Lys9, in the context of nucleosomes but not free acetylated histone H3 protein substrates. By installing a chemical warhead at the Lys9 position of histone H3, we trap a catalytically poised Sirt6 in complex with a nucleosome and employ this in cryo-EM structural analysis. The structure of Sirt6 bound to a nucleosome reveals extensive interactions between distinct segments of Sirt6 and the H2A/H2B acidic patch and nucleosomal DNA, which accounts for the rapid deacetylation of nucleosomal H3 sites and the disfavoring of histone H2B acetylation sites. These findings provide a new framework for understanding how HDACs target and regulate chromatin. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28915.map.gz | 150.9 MB | EMDB map data format | |
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Header (meta data) | emd-28915-v30.xml emd-28915.xml | 30.3 KB 30.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28915_fsc.xml | 11.6 KB | Display | FSC data file |
Images | emd_28915.png | 58.7 KB | ||
Masks | emd_28915_msk_1.map | 163.6 MB | Mask map | |
Filedesc metadata | emd-28915.cif.gz | 6.7 KB | ||
Others | emd_28915_additional_1.map.gz emd_28915_additional_2.map.gz emd_28915_additional_3.map.gz emd_28915_additional_4.map.gz emd_28915_half_map_1.map.gz emd_28915_half_map_2.map.gz | 151.9 MB 154.4 MB 3.2 MB 151.8 MB 151.9 MB 151.9 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28915 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28915 | HTTPS FTP |
-Validation report
Summary document | emd_28915_validation.pdf.gz | 1 MB | Display | EMDB validaton report |
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Full document | emd_28915_full_validation.pdf.gz | 1 MB | Display | |
Data in XML | emd_28915_validation.xml.gz | 20.2 KB | Display | |
Data in CIF | emd_28915_validation.cif.gz | 26.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28915 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28915 | HTTPS FTP |
-Related structure data
Related structure data | 8f86MC M: atomic model generated by this map C: citing same article (ref.) |
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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_28915.map.gz / Format: CCP4 / Size: 163.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | map A | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_28915_msk_1.map | ||||||||||||
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-Additional map: half map 2 for map B
File | emd_28915_additional_1.map | ||||||||||||
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Annotation | half map 2 for map B | ||||||||||||
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-Additional map: map B
File | emd_28915_additional_2.map | ||||||||||||
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Annotation | map B | ||||||||||||
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-Additional map: mask for map B
File | emd_28915_additional_3.map | ||||||||||||
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Annotation | mask for map B | ||||||||||||
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-Additional map: half map 1 for map B
File | emd_28915_additional_4.map | ||||||||||||
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Annotation | half map 1 for map B | ||||||||||||
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-Half map: half map 2 for map A
File | emd_28915_half_map_1.map | ||||||||||||
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Annotation | half map 2 for map A | ||||||||||||
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Density Histograms |
-Half map: half map 1 for map A
File | emd_28915_half_map_2.map | ||||||||||||
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Annotation | half map 1 for map A | ||||||||||||
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Density Histograms |
-Sample components
+Entire : SIRT6 bound to H3K9Ac
+Supramolecule #1: SIRT6 bound to H3K9Ac
+Macromolecule #1: Histone H3.2
+Macromolecule #2: Histone H4
+Macromolecule #3: Histone H2A type 1
+Macromolecule #4: Histone H2B
+Macromolecule #7: NAD-dependent protein deacylase sirtuin-6
+Macromolecule #5: DNA (148-MER)
+Macromolecule #6: DNA (148-MER)
+Macromolecule #8: [(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl...
+Macromolecule #9: ZINC ION
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.45 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.7 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
+Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: RIGID BODY FIT |
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Output model | PDB-8f86: |