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- PDB-9c57: Reconstituted P400 Subcomplex of the human TIP60 complex -

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Entry
Database: PDB / ID: 9c57
TitleReconstituted P400 Subcomplex of the human TIP60 complex
Components
  • Actin, cytoplasmic 1
  • Actin-like protein 6A
  • DNA methyltransferase 1-associated protein 1
  • E1A-binding protein p400
  • Enhancer of polycomb homolog 1
  • RuvB-like 1
  • RuvB-like 2
  • Vacuolar protein sorting-associated protein 72 homolog
KeywordsGENE REGULATION / complex / chromatin regulator
Function / homology
Function and homology information


piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / positive regulation of norepinephrine uptake / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / sperm DNA condensation / histone chaperone activity / establishment of protein localization to chromatin / cellular response to cytochalasin B ...piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / positive regulation of norepinephrine uptake / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / sperm DNA condensation / histone chaperone activity / establishment of protein localization to chromatin / cellular response to cytochalasin B / R2TP complex / bBAF complex / npBAF complex / regulation of transepithelial transport / nBAF complex / brahma complex / dynein axonemal particle / morphogenesis of a polarized epithelium / neural retina development / protein localization to adherens junction / postsynaptic actin cytoskeleton / Swr1 complex / structural constituent of postsynaptic actin cytoskeleton / protein antigen binding / Formation of the dystrophin-glycoprotein complex (DGC) / GBAF complex / Formation of annular gap junctions / Tat protein binding / Gap junction degradation / regulation of G0 to G1 transition / Folding of actin by CCT/TriC / Cell-extracellular matrix interactions / dense body / RPAP3/R2TP/prefoldin-like complex / chromatin-protein adaptor activity / Ino80 complex / regulation of nucleotide-excision repair / Prefoldin mediated transfer of substrate to CCT/TriC / RSC-type complex / apical protein localization / regulation of double-strand break repair / blastocyst formation / box C/D snoRNP assembly / adherens junction assembly / RHOF GTPase cycle / Adherens junctions interactions / tight junction / Sensory processing of sound by outer hair cells of the cochlea / protein folding chaperone complex / Interaction between L1 and Ankyrins / SWI/SNF complex / regulation of mitotic metaphase/anaphase transition / Sensory processing of sound by inner hair cells of the cochlea / positive regulation of T cell differentiation / regulation of norepinephrine uptake / transporter regulator activity / apical junction complex / nitric-oxide synthase binding / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / positive regulation of double-strand break repair / spinal cord development / maintenance of blood-brain barrier / regulation of chromosome organization / NuA4 histone acetyltransferase complex / negative regulation of gene expression, epigenetic / establishment or maintenance of cell polarity / cortical cytoskeleton / spermatid development / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / positive regulation of stem cell population maintenance / Transcriptional Regulation by E2F6 / Regulation of MITF-M-dependent genes involved in pigmentation / Recycling pathway of L1 / regulation of synaptic vesicle endocytosis / regulation of G1/S transition of mitotic cell cycle / regulation of DNA replication / TFIID-class transcription factor complex binding / brush border / regulation of embryonic development / kinesin binding / MLL1 complex / somatic stem cell population maintenance / Telomere Extension By Telomerase / EPH-ephrin mediated repulsion of cells / negative regulation of cell differentiation / RHO GTPases Activate WASPs and WAVEs / enzyme-substrate adaptor activity / positive regulation of myoblast differentiation / RHO GTPases activate IQGAPs / positive regulation of double-strand break repair via homologous recombination / regulation of DNA repair / regulation of protein localization to plasma membrane / RNA polymerase II core promoter sequence-specific DNA binding / DNA helicase activity / cytoskeleton organization / Deposition of new CENPA-containing nucleosomes at the centromere / EPHB-mediated forward signaling / TBP-class protein binding / substantia nigra development / calyx of Held
Similarity search - Function
Enhancer of polycomb, C-terminal / Enhancer of Polycomb C-terminus / DNA methyltransferase 1-associated 1 / DNA methyltransferase 1-associated protein 1 (DMAP1) / E1A-binding protein p400, N-terminal / E1A-binding protein p400, N-terminal / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / Enhancer of polycomb protein ...Enhancer of polycomb, C-terminal / Enhancer of Polycomb C-terminus / DNA methyltransferase 1-associated 1 / DNA methyltransferase 1-associated protein 1 (DMAP1) / E1A-binding protein p400, N-terminal / E1A-binding protein p400, N-terminal / SWR1-complex protein 4/DNA methyltransferase 1-associated protein 1 / DAMP1, SANT/Myb-like domain / SANT/Myb-like domain of DAMP1 / Enhancer of polycomb protein / Vps72/YL1, N-terminal / YL1 nuclear protein / Vps72/YL1, C-terminal / YL1 nuclear protein C-terminal domain / YL1 nuclear protein C-terminal domain / Myb-like domain profile. / domain in helicases and associated with SANT domains / RuvB-like / RuvB-like, AAA-lid domain / RuvBL1/2, DNA/RNA binding domain / TIP49 P-loop domain / TIP49 AAA-lid domain / TIP49, P-loop domain / HSA domain / Helicase/SANT-associated domain / HSA domain profile. / Enhancer of polycomb-like, N-terminal / Enhancer of polycomb-like / : / SNF2-like, N-terminal domain superfamily / SNF2, N-terminal / SNF2-related domain / SANT/Myb domain / Actins signature 1. / Actin, conserved site / Actins signature 2. / Actin/actin-like conserved site / Actins and actin-related proteins signature. / Actin / Actin family / Actin / Helicase conserved C-terminal domain / ATPase, nucleotide binding domain / helicase superfamily c-terminal domain / Superfamilies 1 and 2 helicase C-terminal domain profile. / Superfamilies 1 and 2 helicase ATP-binding type-1 domain profile. / DEAD-like helicases superfamily / Helicase, C-terminal / Helicase superfamily 1/2, ATP-binding domain / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ADENOSINE-5'-TRIPHOSPHATE / Actin-like protein 6A / Actin, cytoplasmic 1 / Vacuolar protein sorting-associated protein 72 homolog / E1A-binding protein p400 / Enhancer of polycomb homolog 1 / DNA methyltransferase 1-associated protein 1 / RuvB-like 2 / RuvB-like 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.75 Å
AuthorsYang, Z. / Mameri, A. / Florez Ariza, A.J. / Cote, J. / Nogales, E.
Funding support United States, Canada, 5items
OrganizationGrant numberCountry
Howard Hughes Medical Institute (HHMI) United States
Canada Research Chairs Canada
Natural Sciences and Engineering Research Council (NSERC, Canada) Canada
Canadian Institutes of Health Research (CIHR) Canada
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) United States
CitationJournal: Science / Year: 2024
Title: Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.
Authors: Zhenlin Yang / Amel Mameri / Claudia Cattoglio / Catherine Lachance / Alfredo Jose Florez Ariza / Jie Luo / Jonathan Humbert / Deepthi Sudarshan / Arul Banerjea / Maxime Galloy / Amélie ...Authors: Zhenlin Yang / Amel Mameri / Claudia Cattoglio / Catherine Lachance / Alfredo Jose Florez Ariza / Jie Luo / Jonathan Humbert / Deepthi Sudarshan / Arul Banerjea / Maxime Galloy / Amélie Fradet-Turcotte / Jean-Philippe Lambert / Jeff A Ranish / Jacques Côté / Eva Nogales /
Abstract: The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) ...The human nucleosome acetyltransferase of histone H4 (NuA4)/Tat-interactive protein, 60 kilodalton (TIP60) coactivator complex, a fusion of the yeast switch/sucrose nonfermentable related 1 (SWR1) and NuA4 complexes, both incorporates the histone variant H2A.Z into nucleosomes and acetylates histones H4, H2A, and H2A.Z to regulate gene expression and maintain genome stability. Our cryo-electron microscopy studies show that, within the NuA4/TIP60 complex, the E1A binding protein P400 (EP400) subunit serves as a scaffold holding the different functional modules in specific positions, creating a distinct arrangement of the actin-related protein (ARP) module. EP400 interacts with the transformation/transcription domain-associated protein (TRRAP) subunit by using a footprint that overlaps with that of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, preventing the formation of a hybrid complex. Loss of the TRRAP subunit leads to mislocalization of NuA4/TIP60, resulting in the redistribution of H2A.Z and its acetylation across the genome, emphasizing the dual functionality of NuA4/TIP60 as a single macromolecular assembly.
History
DepositionJun 5, 2024Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 21, 2024Provider: repository / Type: Initial release
Revision 1.1Sep 4, 2024Group: Data collection / Database references / Category: citation / em_admin / Item: _citation.journal_volume / _em_admin.last_update
Revision 1.2Sep 11, 2024Group: Data collection / Category: em_admin / Item: _em_admin.last_update

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
E: RuvB-like 1
H: Enhancer of polycomb homolog 1
M: Actin-like protein 6A
B: RuvB-like 2
C: RuvB-like 1
D: RuvB-like 2
F: RuvB-like 2
G: E1A-binding protein p400
I: DNA methyltransferase 1-associated protein 1
J: Actin, cytoplasmic 1
K: Vacuolar protein sorting-associated protein 72 homolog
L: Actin-like protein 6A
A: RuvB-like 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)976,73621
Polymers972,56613
Non-polymers4,1708
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Protein , 8 types, 13 molecules ECAHMLBDFGIJK

#1: Protein RuvB-like 1 / 49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa ...49 kDa TATA box-binding protein-interacting protein / 49 kDa TBP-interacting protein / 54 kDa erythrocyte cytosolic protein / ECP-54 / INO80 complex subunit H / Nuclear matrix protein 238 / NMP 238 / Pontin 52 / TIP49a / TIP60-associated protein 54-alpha / TAP54-alpha


Mass: 50296.914 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RUVBL1, INO80H, NMP238, TIP49, TIP49A / Production host: Homo sapiens (human) / References: UniProt: Q9Y265, DNA helicase
#2: Protein Enhancer of polycomb homolog 1


Mass: 93589.172 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EPC1 / Production host: Homo sapiens (human) / References: UniProt: Q9H2F5
#3: Protein Actin-like protein 6A / 53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor ...53 kDa BRG1-associated factor A / Actin-related protein Baf53a / ArpNbeta / BRG1-associated factor 53A / BAF53A / INO80 complex subunit K


Mass: 47509.812 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTL6A, BAF53, BAF53A, INO80K / Production host: Homo sapiens (human) / References: UniProt: O96019
#4: Protein RuvB-like 2 / 48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa ...48 kDa TATA box-binding protein-interacting protein / 48 kDa TBP-interacting protein / 51 kDa erythrocyte cytosolic protein / ECP-51 / INO80 complex subunit J / Repressing pontin 52 / Reptin 52 / TIP49b / TIP60-associated protein 54-beta / TAP54-beta


Mass: 51222.465 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RUVBL2, INO80J, TIP48, TIP49B, CGI-46 / Production host: Homo sapiens (human) / References: UniProt: Q9Y230, DNA helicase
#5: Protein E1A-binding protein p400 / CAG repeat protein 32 / Domino homolog / hDomino / Trinucleotide repeat-containing gene 12 protein ...CAG repeat protein 32 / Domino homolog / hDomino / Trinucleotide repeat-containing gene 12 protein / p400 kDa SWI2/SNF2-related protein


Mass: 343867.312 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EP400, CAGH32, KIAA1498, KIAA1818, TNRC12 / Production host: Homo sapiens (human)
References: UniProt: Q96L91, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#6: Protein DNA methyltransferase 1-associated protein 1 / DNMAP1 / DNMT1-associated protein 1


Mass: 53090.699 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DMAP1, KIAA1425 / Production host: Homo sapiens (human) / References: UniProt: Q9NPF5
#7: Protein Actin, cytoplasmic 1 / Beta-actin


Mass: 41782.660 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTB / Production host: Homo sapiens (human) / References: UniProt: P60709
#8: Protein Vacuolar protein sorting-associated protein 72 homolog / Protein YL-1 / Transcription factor-like 1


Mass: 40658.363 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VPS72, TCFL1, YL1 / Production host: Homo sapiens (human) / References: UniProt: Q15906

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Non-polymers , 2 types, 8 molecules

#9: Chemical
ChemComp-AGS / PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-GAMMA-S / ADENOSINE 5'-(3-THIOTRIPHOSPHATE) / ADENOSINE 5'-(GAMMA-THIOTRIPHOSPHATE) / ADENOSINE-5'-DIPHOSPHATE MONOTHIOPHOSPHATE


Mass: 523.247 Da / Num. of mol.: 7 / Source method: obtained synthetically / Formula: C10H16N5O12P3S / Feature type: SUBJECT OF INVESTIGATION / Comment: ATP-gamma-S, energy-carrying molecule analogue*YM
#10: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Feature type: SUBJECT OF INVESTIGATION / Comment: ATP, energy-carrying molecule*YM

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Details

Has ligand of interestY

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Reconstituted P400 Subcomplex of the human TIP60 complex
Type: COMPLEX / Entity ID: #1-#8 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: SPOT SCAN
Electron lensMode: 4D-STEM / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.20.1_4487: / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.75 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 166442 / Symmetry type: POINT
RefinementCross valid method: NONE

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