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Open data
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Basic information
Entry | Database: PDB / ID: 8of4 | ||||||
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Title | Nucleosome Bound human SIRT6 (Composite) | ||||||
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![]() | GENE REGULATION / Transferase / Deacetylase / Histone H3 deacetylation | ||||||
Function / homology | ![]() NAD-dependent histone H3K56 deacetylase activity / NAD-dependent histone H3K18 deacetylase activity / NAD-dependent histone H3K9 deacetylase activity / protein delipidation / ketone biosynthetic process / regulation of lipid catabolic process / NAD+- protein-lysine ADP-ribosyltransferase activity / chromosome, subtelomeric region / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity ...NAD-dependent histone H3K56 deacetylase activity / NAD-dependent histone H3K18 deacetylase activity / NAD-dependent histone H3K9 deacetylase activity / protein delipidation / ketone biosynthetic process / regulation of lipid catabolic process / NAD+- protein-lysine ADP-ribosyltransferase activity / chromosome, subtelomeric region / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / 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 / retrotransposon silencing / protein acetyllysine N-acetyltransferase / cardiac muscle cell differentiation / positive regulation of chondrocyte proliferation / pericentric heterochromatin formation / positive regulation of telomere maintenance / protein deacetylation / negative regulation of glucose import / protein localization to site of double-strand break / NAD-dependent histone deacetylase activity / TORC2 complex binding / lncRNA binding / negative regulation of glycolytic process / negative regulation of protein localization to chromatin / positive regulation of double-strand break repair / DNA repair-dependent chromatin remodeling / positive regulation of vascular endothelial cell proliferation / negative regulation of protein import into nucleus / negative regulation of gene expression, epigenetic / regulation of double-strand break repair via homologous recombination / positive regulation of stem cell population maintenance / positive regulation of stem cell proliferation / regulation of protein secretion / 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 / Transferases; Glycosyltransferases; Pentosyltransferases / NAD+ ADP-ribosyltransferase activity / NAD+ binding / subtelomeric heterochromatin formation / positive regulation of fat cell differentiation / regulation of protein localization to plasma membrane / pericentric heterochromatin / negative regulation of gluconeogenesis / response to UV / nucleosome binding / 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 / regulation of circadian rhythm / positive regulation of insulin secretion / chromatin DNA binding / Pre-NOTCH Transcription and Translation / structural constituent of chromatin / transcription corepressor activity / nucleosome / positive regulation of fibroblast proliferation / double-strand break repair / nucleosome assembly / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / glucose homeostasis / positive regulation of cold-induced thermogenesis / 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 | ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.94 Å | ||||||
![]() | Smirnova, E. / Bignon, E. / Schultz, P. / Papai, G. / Ben-Shem, A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Binding to nucleosome poises human SIRT6 for histone H3 deacetylation. Authors: Ekaterina Smirnova / Emmanuelle Bignon / Patrick Schultz / Gabor Papai / Adam Ben Shem / ![]() Abstract: Sirtuin 6 (SIRT6) is an NAD-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic ...Sirtuin 6 (SIRT6) is an NAD-dependent histone H3 deacetylase that is prominently found associated with chromatin, attenuates transcriptionally active promoters and regulates DNA repair, metabolic homeostasis and lifespan. Unlike other sirtuins, it has low affinity to free histone tails but demonstrates strong binding to nucleosomes. It is poorly understood how SIRT6 docking on nucleosomes stimulates its histone deacetylation activity. Here, we present the structure of human SIRT6 bound to a nucleosome determined by cryogenic electron microscopy. The zinc finger domain of SIRT6 associates tightly with the acidic patch of the nucleosome through multiple arginine anchors. The Rossmann fold domain binds to the terminus of the looser DNA half of the nucleosome, detaching two turns of the DNA from the histone octamer and placing the NAD binding pocket close to the DNA exit site. This domain shows flexibility with respect to the fixed zinc finger and moves with, but also relative to, the unwrapped DNA terminus. We apply molecular dynamics simulations of the histone tails in the nucleosome to show that in this mode of interaction, the active site of SIRT6 is perfectly poised to catalyze deacetylation of the H3 histone tail and that the partial unwrapping of the DNA allows even lysines close to the H3 core to reach the enzyme. #1: ![]() Title: Binding to nucleosome poises SIRT6 for histone H3 de-acetylation Authors: Smirnova, E. / Bignon, E. / Schultz, P. / Papai, G. / Ben-Shem, A. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 358 KB | Display | ![]() |
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PDB format | ![]() | 265.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 842.6 KB | Display | ![]() |
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Full document | ![]() | 910.1 KB | Display | |
Data in XML | ![]() | 39.5 KB | Display | |
Data in CIF | ![]() | 63.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 16845MC C: citing same article ( M: map data used to model this data |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Components
-Protein , 5 types, 9 molecules AEBFCGDHL
#1: Protein | Mass: 15421.101 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 14093.436 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 13979.291 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | | Mass: 39180.914 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q8N6T7, Transferases; Acyltransferases; Transferring groups other than aminoacyl groups, protein acetyllysine N-acetyltransferase, Transferases; Glycosyltransferases; Pentosyltransferases |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 44520.383 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#6: DNA chain | Mass: 44991.660 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Non-polymers , 1 types, 1 molecules ![](data/chem/img/ZN.gif)
#8: Chemical | ChemComp-ZN / |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Buffer solution | pH: 7.5 | ||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||
Specimen support | Grid material: COPPER/RHODIUM / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R3.5/1 | ||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company | ||||||||||||
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EM imaging | Accelerating voltage: 300 kV / C2 aperture diameter: 50 µm / Cryogen: NITROGEN / Electron source:
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2033169 | ||||||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 439796 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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