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- PDB-8xvt: The core subcomplex of human NuA4/TIP60 complex -

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Basic information

Entry
Database: PDB / ID: 8xvt
TitleThe core subcomplex of human NuA4/TIP60 complex
Components
  • (Isoform 2 of ...) x 2
  • Actin, cytoplasmic 1
  • Actin-like protein 6A
  • DNA methyltransferase 1-associated protein 1
  • RuvB-like 1
  • RuvB-like 2
  • Vacuolar protein sorting-associated protein 72 homolog
KeywordsTRANSCRIPTION / Remodeler / Histone Acetyltransferase Complex / NuA4 / TIP60
Function / homology
Function and homology information


piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / sperm DNA condensation / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / positive regulation of norepinephrine uptake / Regulation of CDH1 Function / Formation of the polybromo-BAF (pBAF) complex / histone chaperone activity ...piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / sperm DNA condensation / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / positive regulation of norepinephrine uptake / Regulation of CDH1 Function / Formation of the polybromo-BAF (pBAF) complex / histone chaperone activity / Formation of the canonical BAF (cBAF) complex / Formation of the non-canonical BAF (ncBAF) complex / Formation of the embryonic stem cell BAF (esBAF) complex / Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) / establishment of protein localization to chromatin / R2TP complex / dynein axonemal particle / bBAF complex / cellular response to cytochalasin B / neural retina development / npBAF complex / nBAF complex / brahma complex / regulation of transepithelial transport / RPAP3/R2TP/prefoldin-like complex / Swr1 complex / morphogenesis of a polarized epithelium / Formation of annular gap junctions / Formation of the dystrophin-glycoprotein complex (DGC) / structural constituent of postsynaptic actin cytoskeleton / GBAF complex / Gap junction degradation / Folding of actin by CCT/TriC / regulation of G0 to G1 transition / Cell-extracellular matrix interactions / protein localization to adherens junction / protein antigen binding / dense body / Tat protein binding / postsynaptic actin cytoskeleton / Ino80 complex / Prefoldin mediated transfer of substrate to CCT/TriC / RSC-type complex / blastocyst formation / regulation of nucleotide-excision repair / regulation of double-strand break repair / Adherens junctions interactions / chromatin-protein adaptor activity / RHOF GTPase cycle / adherens junction assembly / box C/D snoRNP assembly / apical protein localization / Sensory processing of sound by inner hair cells of the cochlea / Sensory processing of sound by outer hair cells of the cochlea / Interaction between L1 and Ankyrins / tight junction / SWI/SNF complex / regulation of mitotic metaphase/anaphase transition / positive regulation of T cell differentiation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / apical junction complex / positive regulation of double-strand break repair / spinal cord development / negative regulation of gene expression, epigenetic / maintenance of blood-brain barrier / regulation of norepinephrine uptake / regulation of chromosome organization / nitric-oxide synthase binding / transporter regulator activity / Transcriptional Regulation by E2F6 / cortical cytoskeleton / positive regulation of stem cell population maintenance / establishment or maintenance of cell polarity / NuA4 histone acetyltransferase complex / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / Recycling pathway of L1 / Regulation of MITF-M-dependent genes involved in pigmentation / TFIID-class transcription factor complex binding / regulation of DNA replication / brush border / MLL1 complex / regulation of G1/S transition of mitotic cell cycle / regulation of embryonic development / somatic stem cell population maintenance / EPH-ephrin mediated repulsion of cells / Telomere Extension By Telomerase / negative regulation of cell differentiation / spermatid development / kinesin binding / protein folding chaperone complex / RHO GTPases Activate WASPs and WAVEs / enzyme-substrate adaptor activity / regulation of synaptic vesicle endocytosis / positive regulation of myoblast differentiation / RNA polymerase II core promoter sequence-specific DNA binding / RHO GTPases activate IQGAPs / regulation of DNA repair / regulation of protein localization to plasma membrane / positive regulation of double-strand break repair via homologous recombination / EPHB-mediated forward signaling
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
ADENOSINE-5'-DIPHOSPHATE / 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: 3.2 Å
AuthorsChen, K. / Wang, L. / Yu, Z. / Yu, J. / Ren, Y. / Wang, Q. / Xu, Y.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2024
Title: Structure of the human TIP60 complex.
Authors: Ke Chen / Li Wang / Zishuo Yu / Jiali Yu / Yulei Ren / Qianmin Wang / Yanhui Xu /
Abstract: Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell ...Mammalian TIP60 is a multi-functional enzyme with histone acetylation and histone dimer exchange activities. It plays roles in diverse cellular processes including transcription, DNA repair, cell cycle control, and embryonic development. Here we report the cryo-electron microscopy structures of the human TIP60 complex with the core subcomplex and TRRAP module refined to 3.2-Å resolution. The structures show that EP400 acts as a backbone integrating the motor module, the ARP module, and the TRRAP module. The RUVBL1-RUVBL2 hexamer serves as a rigid core for the assembly of EP400 ATPase and YL1 in the motor module. In the ARP module, an ACTL6A-ACTB heterodimer and an extra ACTL6A make hydrophobic contacts with EP400 HSA helix, buttressed by network interactions among DMAP1, EPC1, and EP400. The ARP module stably associates with the motor module but is flexibly tethered to the TRRAP module, exhibiting a unique feature of human TIP60. The architecture of the nucleosome-bound human TIP60 reveals an unengaged nucleosome that is located between the core subcomplex and the TRRAP module. Our work illustrates the molecular architecture of human TIP60 and provides architectural insights into how this complex is bound by the nucleosome.
History
DepositionJan 15, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 24, 2024Provider: repository / Type: Initial release
Revision 1.1Jul 31, 2024Group: Data collection / Database references / Category: citation / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.year / _em_admin.last_update
Revision 1.2Sep 4, 2024Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _em_admin.last_update
Revision 1.3Sep 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
A: RuvB-like 1
B: RuvB-like 2
C: RuvB-like 1
D: RuvB-like 2
E: RuvB-like 1
F: RuvB-like 2
G: DNA methyltransferase 1-associated protein 1
H: Isoform 2 of E1A-binding protein p400
I: Actin-like protein 6A
J: Actin-like protein 6A
K: Actin, cytoplasmic 1
M: Isoform 2 of Enhancer of polycomb homolog 1
N: Vacuolar protein sorting-associated protein 72 homolog
hetero molecules


Theoretical massNumber of molelcules
Total (without water)970,14122
Polymers966,29613
Non-polymers3,8459
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 , 6 types, 11 molecules ACEBDFGIJKN

#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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q9Y265, DNA helicase
#2: 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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q9Y230, DNA helicase
#3: 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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q9NPF5
#5: Protein Actin-like protein 6A


Mass: 47509.812 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ACTL6A / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: O96019
#6: 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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
References: UniProt: P60709, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q15906

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Isoform 2 of ... , 2 types, 2 molecules HM

#4: Protein Isoform 2 of 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: 340198.062 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 / Cell line (production host): Expi293F / Production host: Homo sapiens (human)
References: UniProt: Q96L91, Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement
#7: Protein Isoform 2 of Enhancer of polycomb homolog 1


Mass: 90988.273 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EPC1 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q9H2F5

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Non-polymers , 1 types, 9 molecules

#9: Chemical
ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE


Mass: 427.201 Da / Num. of mol.: 9 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Feature type: SUBJECT OF INVESTIGATION / Comment: ADP, 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: The core subcomplex of human NuA4/TIP60 complex / Type: COMPLEX / Entity ID: #1-#8 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 7.4
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: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2800 nm / Nominal defocus min: 1500 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 701594 / Symmetry type: POINT
Atomic model buildingPDB-ID: 6IGM

6igm


Accession code: 6IGM / Source name: PDB / Type: experimental model

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