+Open data
-Basic information
Entry | Database: PDB / ID: 8qr1 | ||||||
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Title | Cryo-EM structure of the human Tip60 complex | ||||||
Components |
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Keywords | TRANSCRIPTION / Eukaryotic transcription / Histone acetyltransferase / chromatin remodeling / Complex | ||||||
Function / homology | Function and homology information ATP-dependent H2AZ histone chaperone activity / piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / positive regulation of norepinephrine uptake / cellular response to cytochalasin B / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / histone chaperone activity / regulation of transepithelial transport / sperm DNA condensation ...ATP-dependent H2AZ histone chaperone activity / piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / positive regulation of norepinephrine uptake / cellular response to cytochalasin B / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / histone chaperone activity / regulation of transepithelial transport / sperm DNA condensation / establishment of protein localization to chromatin / morphogenesis of a polarized epithelium / bBAF complex / postsynaptic actin cytoskeleton organization / npBAF complex / nBAF complex / protein localization to adherens junction / postsynaptic actin cytoskeleton / brahma complex / dynein axonemal particle / Tat protein binding / R2TP complex / structural constituent of postsynaptic actin cytoskeleton / RPAP3/R2TP/prefoldin-like complex / chromatin-protein adaptor activity / GBAF complex / regulation of G0 to G1 transition / neural retina development / Formation of annular gap junctions / dense body / Gap junction degradation / Swr1 complex / Cell-extracellular matrix interactions / positive regulation of telomerase RNA localization to Cajal body / Folding of actin by CCT/TriC / apical protein localization / regulation of double-strand break repair / regulation of nucleotide-excision repair / RSC-type complex / adherens junction assembly / Ino80 complex / Prefoldin mediated transfer of substrate to CCT/TriC / blastocyst formation / RHOF GTPase cycle / Adherens junctions interactions / tight junction / enzyme-substrate adaptor activity / Sensory processing of sound by outer hair cells of the cochlea / regulation of mitotic metaphase/anaphase transition / protein folding chaperone complex / Interaction between L1 and Ankyrins / Sensory processing of sound by inner hair cells of the cochlea / SWI/SNF complex / positive regulation of double-strand break repair / regulation of norepinephrine uptake / box C/D snoRNP assembly / positive regulation of T cell differentiation / regulation of synaptic vesicle endocytosis / apical junction complex / establishment or maintenance of cell polarity / regulation of cyclin-dependent protein serine/threonine kinase activity / cortical cytoskeleton / maintenance of blood-brain barrier / negative regulation of gene expression, epigenetic / spinal cord development / positive regulation of stem cell population maintenance / regulation of chromosome organization / NuA4 histone acetyltransferase complex / nitric-oxide synthase binding / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / Regulation of MITF-M-dependent genes involved in pigmentation / regulation of DNA replication / regulation of G1/S transition of mitotic cell cycle / Transcriptional Regulation by E2F6 / somatic stem cell population maintenance / Recycling pathway of L1 / brush border / kinesin binding / calyx of Held / TFIID-class transcription factor complex binding / regulation of embryonic development / negative regulation of cell differentiation / spermatid development / MLL1 complex / Telomere Extension By Telomerase / positive regulation of double-strand break repair via homologous recombination / EPH-ephrin mediated repulsion of cells / positive regulation of myoblast differentiation / RHO GTPases Activate WASPs and WAVEs / regulation of protein localization to plasma membrane / RNA polymerase II core promoter sequence-specific DNA binding / RHO GTPases activate IQGAPs / regulation of DNA repair / histone acetyltransferase activity / Deposition of new CENPA-containing nucleosomes at the centromere / substantia nigra development / EPHB-mediated forward signaling / TBP-class protein binding / positive regulation of DNA repair / telomere maintenance Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||
Authors | Li, C. / Smirnova, E. / Schnitzler, C. / Crucifix, C. / Concordet, J.P. / Brion, A. / Poterszman, A. / Schultz, P. / Papai, G. / Ben-Shem, A. | ||||||
Funding support | France, 1items
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Citation | Journal: Nature / Year: 2024 Title: Structure of human TIP60-C histone exchange and acetyltransferase complex. Authors: Changqing Li / Ekaterina Smirnova / Charlotte Schnitzler / Corinne Crucifix / Jean Paul Concordet / Alice Brion / Arnaud Poterszman / Patrick Schultz / Gabor Papai / Adam Ben-Shem / Abstract: Chromatin structure is a key regulator of DNA transcription, replication, and repair. In humans, the TIP60/EP400 complex (TIP60-C) is a 20-subunit assembly that impacts chromatin structure via two ...Chromatin structure is a key regulator of DNA transcription, replication, and repair. In humans, the TIP60/EP400 complex (TIP60-C) is a 20-subunit assembly that impacts chromatin structure via two enzymatic activities: ATP-dependent exchange of histone H2A/H2B for H2A.Z/H2B and histone acetylation, which in yeast are carried out by two independent complexes, SWR1 and NuA4, respectively. How these activities are merged in humans into one super-complex and what this association entails for their structure, mechanism and recruitment to chromatin is unknown. Here we describe the 2.4-3.3 Å resolution structure of the endogenous human TIP60-C. We find a three lobed architecture composed of SWR1-like (SWR1L) and NuA4-like (NuA4L) parts, that associate with a TRRAP activator-binding module. The huge EP400 subunit harbors the ATPase motor, traverses twice the junction between SWR1L and NuA4L, and constitutes the scaffold of the three-lobed architecture. NuA4L is completely re-arranged compared to its yeast counterpart. TRRAP is flexibly tethered to NuA4L, in stark contrast to its robust connection to the complete opposite side of yeast NuA4. A modeled nucleosome bound to SWR1L, supported by activity tests, suggests that some aspects of the histone exchange mechanism diverge from the yeast example. Furthermore, a fixed actin module, as opposed to the mobile actin subcomplex in SWR1, the flexibility of TRRAP and the weak effect of extra-nucleosomal DNA on exchange activity, lead to a different, activator-based, mode of enlisting TIP60-C to chromatin. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8qr1.cif.gz | 1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8qr1.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8qr1.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8qr1_validation.pdf.gz | 974.1 KB | Display | wwPDB validaton report |
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Full document | 8qr1_full_validation.pdf.gz | 986.6 KB | Display | |
Data in XML | 8qr1_validation.xml.gz | 113.9 KB | Display | |
Data in CIF | 8qr1_validation.cif.gz | 184.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qr/8qr1 ftp://data.pdbj.org/pub/pdb/validation_reports/qr/8qr1 | HTTPS FTP |
-Related structure data
Related structure data | 18611MC 8qriC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 8 types, 13 molecules ACFSBGKLIEHDJ
#1: Protein | Mass: 343867.312 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 References: UniProt: Q96L91, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement | ||||||
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#2: Protein | Mass: 93589.172 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9H2F5 | ||||||
#3: Protein | Mass: 53090.699 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9NPF5 | ||||||
#4: Protein | Mass: 40658.363 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q15906 | ||||||
#5: Protein | Mass: 41782.660 Da / Num. of mol.: 2 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: P60709 #6: Protein | | Mass: 47509.812 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: O96019 #7: Protein | Mass: 50296.914 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9Y265, DNA helicase #8: Protein | Mass: 51222.465 Da / Num. of mol.: 3 / Source method: isolated from a natural source / Source: (natural) Homo sapiens (human) / Cell line: K562 / References: UniProt: Q9Y230, DNA helicase |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Tip60 complex / Type: CELL / Entity ID: all / Source: NATURAL | ||||||||||||||||||||||||||||||||
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Source (natural) | Organism: Homo sapiens (human) / Strain: K562 / Cellular location: nucleus | ||||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 279 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM | ||||||||||||
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE | ||||||||||||
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER | ||||||||||||
Image recording |
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-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 284286 | ||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 180397 / Symmetry type: POINT | ||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL |