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Open data
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Basic information
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Title | Nucleosome Bound human SIRT6 (composite structure) | |||||||||
![]() | Composite map | |||||||||
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Function / homology | ![]() NAD-dependent histone H3K56 deacetylase activity / NAD-dependent histone H3K18 deacetylase activity / ketone biosynthetic process / NAD-dependent histone H3K9 deacetylase activity / protein delipidation / regulation of lipid catabolic process / NAD+- protein-lysine ADP-ribosyltransferase activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 38.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 23.7 KB 23.7 KB | Display Display | ![]() |
Images | ![]() | 97.2 KB | ||
Filedesc metadata | ![]() | 7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8of4MC C: citing same article ( M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | Composite map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.916 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
+Entire : Human Sirtuin 6 in complex with the nucleosome
+Supramolecule #1: Human Sirtuin 6 in complex with the nucleosome
+Supramolecule #2: SIRT6
+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 (145-MER)
+Macromolecule #6: DNA (145-MER)
+Macromolecule #8: ZINC ION
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Grid | Model: Quantifoil R3.5/1 / Material: COPPER/RHODIUM / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy #1
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Microscopy ID | 1 |
Image recording | Image recording ID: 1 / Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Electron microscopy #1~
Microscope | TFS KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Specialist optics | Energy filter - Name: GIF Quantum LS / Energy filter - Slit width: 20 eV |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Microscopy ID | 1 |
Image recording | Image recording ID: 2 / Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 55.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 2033169 |
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Startup model | Type of model: OTHER / Details: Ab-initio in cryoSPARC |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC |
Final 3D classification | Number classes: 10 / Software - Name: RELION |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC |
Final reconstruction | Algorithm: BACK PROJECTION / Resolution.type: BY AUTHOR / Resolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 439796 |
Image recording ID | 1 |