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- PDB-8xvg: Structure of human NuA4/TIP60 complex -

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Entry
Database: PDB / ID: 8xvg
TitleStructure of human NuA4/TIP60 complex
Components
  • (Isoform 2 of ...) x 3
  • ACTB protein (Fragment)
  • 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 / 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 / transcription factor TFTC complex / R2TP complex ...piccolo histone acetyltransferase complex / promoter-enhancer loop anchoring activity / telomerase RNA localization to Cajal body / 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 / transcription factor TFTC complex / R2TP complex / npBAF complex / brahma complex / dynein axonemal particle / neural retina development / Swr1 complex / protein antigen binding / GBAF complex / regulation of G0 to G1 transition / RPAP3/R2TP/prefoldin-like complex / chromatin-protein adaptor activity / Ino80 complex / regulation of nucleotide-excision repair / RSC-type complex / regulation of double-strand break repair / blastocyst formation / box C/D snoRNP assembly / protein folding chaperone complex / SAGA complex / SWI/SNF complex / regulation of mitotic metaphase/anaphase transition / positive regulation of T cell differentiation / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / positive regulation of double-strand break repair / spinal cord development / DNA repair-dependent chromatin remodeling / regulation of chromosome organization / NuA4 histone acetyltransferase complex / negative regulation of gene expression, epigenetic / spermatid development / RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known / positive regulation of stem cell population maintenance / regulation of RNA splicing / Transcriptional Regulation by E2F6 / Regulation of MITF-M-dependent genes involved in pigmentation / regulation of G1/S transition of mitotic cell cycle / regulation of DNA replication / TFIID-class transcription factor complex binding / regulation of embryonic development / MLL1 complex / somatic stem cell population maintenance / Telomere Extension By Telomerase / negative regulation of cell differentiation / enzyme-substrate adaptor activity / positive regulation of myoblast differentiation / positive regulation of double-strand break repair via homologous recombination / regulation of DNA repair / RNA polymerase II core promoter sequence-specific DNA binding / DNA helicase activity / Deposition of new CENPA-containing nucleosomes at the centromere / TBP-class protein binding / telomere maintenance / transcription initiation-coupled chromatin remodeling / positive regulation of DNA repair / replication fork / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / helicase activity / positive regulation of cell differentiation / transcription coregulator activity / cellular response to estradiol stimulus / Formation of the beta-catenin:TCF transactivating complex / negative regulation of canonical Wnt signaling pathway / double-strand break repair via homologous recombination / euchromatin / DNA Damage Recognition in GG-NER / beta-catenin binding / ADP binding / DNA Damage/Telomere Stress Induced Senescence / kinetochore / Hydrolases; Acting on acid anhydrides; Acting on acid anhydrides to facilitate cellular and subcellular movement / chromatin DNA binding / RMTs methylate histone arginines / positive regulation of protein import into nucleus / nuclear matrix / transcription corepressor activity / cellular response to UV / UCH proteinases / positive regulation of canonical Wnt signaling pathway / nucleosome / unfolded protein binding / nervous system development / protein folding / chromatin organization / site of double-strand break / HATs acetylate histones / ATPase binding / regulation of apoptotic process / DNA recombination / spermatogenesis / nuclear membrane / DNA helicase
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 / Tra1, HEAT repeat ring region / Tra1, HEAT repeat central region / YL1 nuclear protein / Tra1 HEAT repeat central region / Tra1 HEAT repeat ring region / 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. / : / PIK-related kinase, FAT / FAT domain / FATC / FATC domain / PIK-related kinase / FAT domain profile. / FATC 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 / Phosphoinositide 3-kinase, catalytic domain / Phosphatidylinositol 3- and 4-kinase / Phosphatidylinositol 3- and 4-kinases catalytic domain profile. / Phosphatidylinositol 3-/4-kinase, catalytic 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 / Armadillo-like helical / 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 / Armadillo-type fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / Protein kinase-like domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
ADENOSINE-5'-DIPHOSPHATE / INOSITOL HEXAKISPHOSPHATE / ACTB protein / Actin-like protein 6A / 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 / Transformation/transcription domain-associated protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 9.4 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
L: Isoform 2 of Transformation/transcription domain-associated protein
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: ACTB protein (Fragment)
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)1,405,75124
Polymers1,401,24614
Non-polymers4,50510
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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Isoform 2 of ... , 3 types, 3 molecules LHM

#1: Protein Isoform 2 of Transformation/transcription domain-associated protein / 350/400 kDa PCAF-associated factor / PAF350/400 / STAF40 / Tra1 homolog


Mass: 434949.906 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRRAP, PAF400 / Cell line (production host): Expi293F / Production host: Homo sapiens (human) / References: UniProt: Q9Y4A5
#5: 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
#8: 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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Protein , 6 types, 11 molecules ACEBDFGIJKN

#2: 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
#3: 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
#4: 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
#6: 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
#7: Protein ACTB protein (Fragment)


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: A0A7K5XZZ2
#9: 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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Non-polymers , 2 types, 10 molecules

#10: Chemical ChemComp-IHP / INOSITOL HEXAKISPHOSPHATE / MYO-INOSITOL HEXAKISPHOSPHATE / INOSITOL 1,2,3,4,5,6-HEXAKISPHOSPHATE


Mass: 660.035 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C6H18O24P6 / Feature type: SUBJECT OF INVESTIGATION
#11: 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: Structure of human NuA4/TIP60 complex / Type: COMPLEX / Entity ID: #2-#7, #1, #8-#9 / 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: 9.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 20275 / Symmetry type: POINT

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