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Open data
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Basic information
Entry | Database: PDB / ID: 9gmr | ||||||||||||||||||||||||
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Title | SIRT7-H3K36MTUnucleosome complex | ||||||||||||||||||||||||
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![]() | DNA / nucleosome complex | ||||||||||||||||||||||||
Function / homology | ![]() regulation of transcription of nucleolar large rRNA by RNA polymerase I / nucleolus organizer region / protein depropionylation / NAD-dependent protein-lysine depropionylase activity / protein deglutarylation / protein-glutaryllysine deglutarylase activity / histone H3K18 deacetylase activity, NAD-dependent / protein-succinyllysine desuccinylase activity / R-loop processing / homologous chromosome pairing at meiosis ...regulation of transcription of nucleolar large rRNA by RNA polymerase I / nucleolus organizer region / protein depropionylation / NAD-dependent protein-lysine depropionylase activity / protein deglutarylation / protein-glutaryllysine deglutarylase activity / histone H3K18 deacetylase activity, NAD-dependent / protein-succinyllysine desuccinylase activity / R-loop processing / homologous chromosome pairing at meiosis / protein methyltransferase activity / NAD-dependent protein lysine deacetylase activity / transposable element silencing / protein acetyllysine N-acetyltransferase / positive regulation of rRNA processing / protein deacetylation / regulation of protein export from nucleus / regulation of mitochondrion organization / DNA repair-dependent chromatin remodeling / positive regulation of transcription by RNA polymerase I / rRNA transcription / NAD+ binding / negative regulation of tumor necrosis factor-mediated signaling pathway / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / regulation of DNA repair / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / negative regulation of protein ubiquitination / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / positive regulation of gluconeogenesis / telomere organization / Interleukin-7 signaling / Inhibition of DNA recombination at telomere / RNA Polymerase I Promoter Opening / Meiotic synapsis / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / Assembly of the ORC complex at the origin of replication / transcription initiation-coupled chromatin remodeling / SUMOylation of chromatin organization proteins / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / SIRT1 negatively regulates rRNA expression / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / innate immune response in mucosa / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / HDMs demethylate histones / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / Nonhomologous End-Joining (NHEJ) / lipopolysaccharide binding / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / G2/M DNA damage checkpoint / Metalloprotease DUBs / NoRC negatively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / B-WICH complex positively regulates rRNA expression / PKMTs methylate histone lysines / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / Transcriptional regulation of granulopoiesis / UCH proteinases / HCMV Early Events / osteoblast differentiation / antimicrobial humoral immune response mediated by antimicrobial peptide / structural constituent of chromatin / antibacterial humoral response / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / nucleosome / heterochromatin formation / site of double-strand break / RUNX1 regulates transcription of genes involved in differentiation of HSCs / nucleosome assembly / Processing of DNA double-strand break ends / HATs acetylate histones / chromatin organization / Senescence-Associated Secretory Phenotype (SASP) / Factors involved in megakaryocyte development and platelet production / MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.8 Å | ||||||||||||||||||||||||
![]() | Moreno-Yruela, C. / Ekundayo, B. / Foteva, P. / Calvino-Sanles, E. / Ni, D. / Stahlberg, H. / Fierz, B. | ||||||||||||||||||||||||
Funding support | ![]() ![]() ![]()
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![]() | ![]() Title: Structural basis of SIRT7 nucleosome engagement and substrate specificity. Authors: Carlos Moreno-Yruela / Babatunde E Ekundayo / Polina N Foteva / Dongchun Ni / Esther Calvino-Sanles / Henning Stahlberg / Beat Fierz / ![]() Abstract: Chromatin-modifying enzymes target distinct residues within histones to finetune gene expression profiles. SIRT7 is an NAD-dependent deacylase often deregulated in cancer, which deacetylates either ...Chromatin-modifying enzymes target distinct residues within histones to finetune gene expression profiles. SIRT7 is an NAD-dependent deacylase often deregulated in cancer, which deacetylates either H3 lysine 36 (H3K36) or H3K18 with high specificity within nucleosomes. Here, we report structures of nucleosome-bound SIRT7, and uncover the structural basis of its specificity towards H3K36 and K18 deacylation, combining a mechanism-based cross-linking strategy, cryo-EM, and enzymatic and cellular assays. We show that the SIRT7 N-terminus represents a unique, extended nucleosome-binding domain, reaching across the nucleosomal surface to the acidic patch. The catalytic domain binds at the H3-tail exit site, engaging both DNA gyres of the nucleosome. Contacting H3K36 versus H3K18 requires a change in binding pose, and results in structural changes in both SIRT7 and the nucleosome. These structures reveal the basis of lysine specificity, allowing us to engineer SIRT7 towards enhanced H3K18ac selectivity, and provides a basis for small molecule modulator development. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 391.4 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 51.2 KB | Display | |
Data in CIF | ![]() | 80 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 51453MC ![]() 9gmkC 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 AEBFCGDHK
#1: Protein | Mass: 15421.101 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H3C15, HIST2H3A, H3C14, H3F2, H3FM, HIST2H3C, H3C13, HIST2H3D Production host: ![]() ![]() #2: Protein | Mass: 11394.426 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, ...Gene: H4C1, H4/A, H4FA, HIST1H4A, H4C2, H4/I, H4FI, HIST1H4B, H4C3, H4/G, H4FG, HIST1H4C, H4C4, H4/B, H4FB, HIST1H4D, H4C5, H4/J, H4FJ, HIST1H4E, H4C6, H4/C, H4FC, HIST1H4F, H4C8, H4/H, H4FH, HIST1H4H, H4C9, H4/M, H4FM, HIST1H4I, H4C11, H4/E, H4FE, HIST1H4J, H4C12, H4/D, H4FD, HIST1H4K, H4C13, H4/K, H4FK, HIST1H4L, H4C14, H4/N, H4F2, H4FN, HIST2H4, HIST2H4A, H4C15, H4/O, H4FO, HIST2H4B, H4C16, H4-16, HIST4H4 Production host: ![]() ![]() #3: Protein | Mass: 13994.354 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #4: Protein | Mass: 13907.226 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #7: Protein | | Mass: 45035.590 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: Q9NRC8, protein acetyllysine N-acetyltransferase, Transferases; Acyltransferases; Transferring groups other than aminoacyl groups |
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-DNA chain , 2 types, 2 molecules IJ
#5: DNA chain | Mass: 45701.125 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#6: DNA chain | Mass: 46283.469 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Non-polymers , 2 types, 2 molecules 
#8: Chemical | ChemComp-A1IY0 / [[( Mass: 673.528 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H33N7O13P2S / Feature type: SUBJECT OF INVESTIGATION |
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#9: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | Y |
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Has protein modification | Y |
-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: K36 structure / Type: COMPLEX / Entity ID: #1-#7 / Source: RECOMBINANT |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 8 |
Specimen | Conc.: 1 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1200 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 |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
EM imaging optics | Energyfilter name: TFS Selectris X |
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Processing
EM software | Name: PHENIX / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 337476 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||
Refinement | Highest resolution: 2.8 Å Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
Refine LS restraints |
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