+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-16842 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | SIRT6 bound nucleosome | |||||||||
Map data | Sharpened map | |||||||||
Sample |
| |||||||||
Keywords | Transferase / Deacetylase / Histone H3 deacetylation / GENE REGULATION | |||||||||
Function / homology | Function and homology information 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 / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / NAD+-protein-arginine ADP-ribosyltransferase 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 / NAD-dependent protein demyristoylase activity / NAD-dependent protein depalmitoylase activity / NAD+-protein-arginine ADP-ribosyltransferase activity / positive regulation of protein localization to chromatin / chromosome, subtelomeric region / 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 / NAD-dependent histone deacetylase activity / protein deacetylation / negative regulation of glucose import / protein localization to site of double-strand break / TORC2 complex binding / negative regulation of glycolytic process / negative regulation of protein localization to chromatin / lncRNA binding / DNA repair-dependent chromatin remodeling / positive regulation of double-strand break repair / 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 / positive regulation of fat cell differentiation / regulation of protein localization to plasma membrane / 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 proteasomal ubiquitin-dependent protein catabolic process / nucleosome assembly / 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 | Homo sapiens (human) / Xenopus laevis (African clawed frog) / synthetic construct (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.94 Å | |||||||||
Authors | Smirnova E / Bignon E / Schultz P / Papai G / Ben-Shem A | |||||||||
Funding support | France, 1 items
| |||||||||
Citation | Journal: Elife / Year: 2024 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: Journal: Elife / Year: 2023 Title: Binding to nucleosome poises SIRT6 for histone H3 de-acetylation Authors: Smirnova E / Bignon E / Schultz P / Papai G / Ben-Shem A | |||||||||
History |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_16842.map.gz | 38.7 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-16842-v30.xml emd-16842.xml | 23.2 KB 23.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_16842_fsc.xml | 7.4 KB | Display | FSC data file |
Images | emd_16842.png | 95.5 KB | ||
Masks | emd_16842_msk_1.map | 42.9 MB | Mask map | |
Filedesc metadata | emd-16842.cif.gz | 5.9 KB | ||
Others | emd_16842_half_map_1.map.gz emd_16842_half_map_2.map.gz | 39.8 MB 39.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-16842 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16842 | HTTPS FTP |
-Related structure data
Related structure data | 8of4C C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_16842.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.916 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_16842_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map A
File | emd_16842_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: Half map B
File | emd_16842_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | Half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : Human Sirtuin 6 in complex with the nucleosome
+Supramolecule #1: Human Sirtuin 6 in complex with the nucleosome
+Supramolecule #2: Human NAD-dependent protein deacylase sirtuin-6
+Supramolecule #3: Histones
+Supramolecule #4: DNA
+Macromolecule #1: Human NAD-dependent protein deacylase sirtuin-6
+Macromolecule #2: Histone H2A
+Macromolecule #3: Histone H2B
+Macromolecule #4: Histone H3
+Macromolecule #5: Histone H4
+Macromolecule #6: DNA (145-MER)
+Macromolecule #7: DNA (145-MER)
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.5 |
---|---|
Grid | Model: Quantifoil R3.5/1 / Material: COPPER/RHODIUM / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS / Support film - Film thickness: 2 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 90 sec. |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Specialist optics | Energy filter - Name: TFS Selectris X / Energy filter - Slit width: 10 eV |
Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.6 µm / Nominal defocus min: 1.2 µm / Nominal magnification: 270000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |