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Open data
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Basic information
Entry | Database: PDB / ID: 8g57 | |||||||||||||||
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Title | Structure of nucleosome-bound Sirtuin 6 deacetylase | |||||||||||||||
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![]() | TRANSFERASE/DNA / Nucleosome / Sirt6 / aging / DNA damage / repair / deacetylation / diacylation / apo / chromatin / heterochromatin / GENE REGULATION / TRANSFERASE-DNA complex | |||||||||||||||
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+-protein poly-ADP-ribosyltransferase activity / negative regulation of tumor necrosis factor-mediated signaling pathway / NAD+ binding / subtelomeric heterochromatin formation / positive regulation of fat cell differentiation / regulation of protein localization to plasma membrane / protein localization to CENP-A containing chromatin / pericentric heterochromatin / negative regulation of gluconeogenesis / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / heterochromatin organization / Packaging Of Telomere Ends / response to UV / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / nucleosome binding / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / RNA Polymerase I Promoter Opening / nucleotidyltransferase activity / Assembly of the ORC complex at the origin of replication / DNA methylation / Condensation of Prophase Chromosomes / positive regulation of protein export from nucleus / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / PRC2 methylates histones and DNA / innate immune response in mucosa / Defective pyroptosis / HDACs deacetylate histones / determination of adult lifespan / RNA Polymerase I Promoter Escape / lipopolysaccharide binding / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / protein destabilization / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / B-WICH complex positively regulates rRNA expression / base-excision repair / G2/M DNA damage checkpoint / regulation of circadian rhythm / positive regulation of insulin secretion / DNA Damage/Telomere Stress Induced Senescence Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() synthetic construct (others) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.07 Å | |||||||||||||||
![]() | Chio, U.S. / Rechiche, O. / Bryll, A.R. / Zhu, J. / Feldman, J.L. / Peterson, C.L. / Tan, S. / Armache, J.-P. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of the human Sirtuin 6-nucleosome complex. Authors: Un Seng Chio / Othman Rechiche / Alysia R Bryll / Jiang Zhu / Erik M Leith / Jessica L Feldman / Craig L Peterson / Song Tan / Jean-Paul Armache / ![]() Abstract: Sirtuin 6 (SIRT6) is a multifaceted protein deacetylase/deacylase and a major target for small-molecule modulators of longevity and cancer. In the context of chromatin, SIRT6 removes acetyl groups ...Sirtuin 6 (SIRT6) is a multifaceted protein deacetylase/deacylase and a major target for small-molecule modulators of longevity and cancer. In the context of chromatin, SIRT6 removes acetyl groups from histone H3 in nucleosomes, but the molecular basis for its nucleosomal substrate preference is unknown. Our cryo-electron microscopy structure of human SIRT6 in complex with the nucleosome shows that the catalytic domain of SIRT6 pries DNA from the nucleosomal entry-exit site and exposes the histone H3 N-terminal helix, while the SIRT6 zinc-binding domain binds to the histone acidic patch using an arginine anchor. In addition, SIRT6 forms an inhibitory interaction with the C-terminal tail of histone H2A. The structure provides insights into how SIRT6 can deacetylate both H3 K9 and H3 K56. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 346.6 KB | Display | ![]() |
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PDB format | ![]() | 260.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.1 MB | Display | ![]() |
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Full document | ![]() | 1.1 MB | Display | |
Data in XML | ![]() | 44.5 KB | Display | |
Data in CIF | ![]() | 68.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 29735MC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Protein , 5 types, 9 molecules KAEBFCGDH
#1: Protein | Mass: 39708.508 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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#2: Protein | Mass: 15004.579 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | Mass: 9704.396 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 14034.355 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #5: Protein | Mass: 13804.045 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-DNA chain , 2 types, 2 molecules IJ
#6: DNA chain | Mass: 46541.637 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
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#7: DNA chain | Mass: 46061.348 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) |
-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
Component | Name: Sirt6 deacetylase bound to a nucleosome assembled with 172-bp 601 Widom DNA Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES | |||||||||||||||||||||||||
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Molecular weight | Value: 300 kDa/nm / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 7.5 Details: 12.5 mM HEPES pH 7.5, 60 mM KCl, 1.5% glycerol, 1 mM DTT | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 1.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: SIRT6 deacetylase bound to asymmetrical nucleosome with 172 DNA base-pairs | |||||||||||||||||||||||||
Specimen support | Details: Glass slides were wrapped with fresh parafilm. Tweezers were washed with ethanol, dried, and then used to pick grids from a grid box. Grids were carefully examined and placed on the parafilm- ...Details: Glass slides were wrapped with fresh parafilm. Tweezers were washed with ethanol, dried, and then used to pick grids from a grid box. Grids were carefully examined and placed on the parafilm-covered slides. These slides were then placed into the PelCO easyGLOW glow discharger, and treated there. Grid material: COPPER / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R2/2 | |||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277.15 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Calibrated magnification: 81000 X / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 nm / Calibrated defocus min: 1000 nm / Calibrated defocus max: 2200 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Temperature (max): 75 K / Temperature (min): 64 K |
Image recording | Average exposure time: 3.3 sec. / Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 2 / Num. of real images: 11872 Details: Data was collected in Super Resolution mode, thus the image size is 11520 (width) x 8184 (height) |
EM imaging optics | Energyfilter slit width: 20 eV / Phase plate: OTHER |
Image scans | Sampling size: 5 µm / Width: 5760 / Height: 4092 |
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Processing
Software | Name: PHENIX / Version: 1.20.1_4487: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Details: CTF was estimated using Patch CTF estimation (multi), and was applied during the refinement Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 12821862 / Details: Particles were selected using Blob Picker | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.07 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 71603 / Algorithm: BACK PROJECTION / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 79 / Protocol: FLEXIBLE FIT / Space: REAL Details: UCSF Chimera was used for manual fitting of the models; It was then used for optimizing the fit by using option Fit in Map. Then Coot was used to analyze the fits, build and adjust the ...Details: UCSF Chimera was used for manual fitting of the models; It was then used for optimizing the fit by using option Fit in Map. Then Coot was used to analyze the fits, build and adjust the models into the existing densities, and refine parts of the model. Once the model has been built, validated and adjusted, we used phenix.real_space_refine to fix and improve the fit into the densities | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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