+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-18794 | |||||||||
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Title | Human Tip60 complex with bound H2A.Z/H2B | |||||||||
Map data | Human Tip60 | |||||||||
Sample |
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Keywords | Eukaryotic transcription / Histone acetyltransferase / chromatin remodeling / Complex / TRANSCRIPTION | |||||||||
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 / heterochromatin / Replacement of protamines by nucleosomes in the male pronucleus / regulation of DNA repair / Packaging Of Telomere Ends / histone acetyltransferase activity / 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 Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 6.2 Å | |||||||||
Authors | Li C / Smirnova E / Schnitzler C / Crucifix C / Concordet JP / Brion A / Poterszman A / Schultz P / Papai G / Ben-Shem A | |||||||||
Funding support | France, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_18794.map.gz | 32.1 MB | EMDB map data format | |
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Header (meta data) | emd-18794-v30.xml emd-18794.xml | 28.8 KB 28.8 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_18794_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_18794.png | 62.9 KB | ||
Masks | emd_18794_msk_1.map | 64 MB | Mask map | |
Filedesc metadata | emd-18794.cif.gz | 9.2 KB | ||
Others | emd_18794_half_map_1.map.gz emd_18794_half_map_2.map.gz | 59.5 MB 59.5 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-18794 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-18794 | HTTPS FTP |
-Validation report
Summary document | emd_18794_validation.pdf.gz | 860.5 KB | Display | EMDB validaton report |
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Full document | emd_18794_full_validation.pdf.gz | 860 KB | Display | |
Data in XML | emd_18794_validation.xml.gz | 16 KB | Display | |
Data in CIF | emd_18794_validation.cif.gz | 21.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18794 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-18794 | HTTPS FTP |
-Related structure data
Related structure data | 8qr1C 8qriC C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_18794.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | Human Tip60 | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.8856 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_18794_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: Half map B
File | emd_18794_half_map_1.map | ||||||||||||
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Annotation | Half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half map A
File | emd_18794_half_map_2.map | ||||||||||||
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Annotation | Half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : Tip60 complex
+Supramolecule #1: Tip60 complex
+Macromolecule #1: EP400
+Macromolecule #2: EPC1
+Macromolecule #3: YL1/VPS72
+Macromolecule #4: DMAP1
+Macromolecule #5: ACL6A
+Macromolecule #6: ACTIN
+Macromolecule #7: RUVBL1
+Macromolecule #8: RUVBL2
+Macromolecule #9: H2A.Z
+Macromolecule #10: H2B
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.2 mg/mL | ||||||||||||||||
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Buffer | pH: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Pretreatment - Type: PLASMA CLEANING / Pretreatment - Time: 90 sec. | ||||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 279 K / Instrument: FEI VITROBOT MARK IV |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal defocus max: 3.4 µm / Nominal defocus min: 1.5 µm |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |