+Open data
-Basic information
Entry | Database: PDB / ID: 6qi9 | ||||||||||||
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Title | Truncated human R2TP complex, structure 4 (ADP-empty) | ||||||||||||
Components |
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Keywords | CHAPERONE / R2TP / HSP90 co-chaperone / PIH1D1 / RPAP3 / RUVBL1 / RUVBL2 / cryo-EM | ||||||||||||
Function / homology | Function and homology information promoter-enhancer loop anchoring activity / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / establishment of protein localization to chromatin / R2TP complex / dynein axonemal particle / RPAP3/R2TP/prefoldin-like complex / Swr1 complex / positive regulation of telomerase RNA localization to Cajal body / regulation of double-strand break repair ...promoter-enhancer loop anchoring activity / regulation of DNA strand elongation / positive regulation of telomere maintenance in response to DNA damage / establishment of protein localization to chromatin / R2TP complex / dynein axonemal particle / RPAP3/R2TP/prefoldin-like complex / Swr1 complex / positive regulation of telomerase RNA localization to Cajal body / regulation of double-strand break repair / Ino80 complex / Telomere Extension By Telomerase / protein folding chaperone complex / box C/D snoRNP assembly / regulation of chromosome organization / NuA4 histone acetyltransferase complex / regulation of DNA replication / TFIID-class transcription factor complex binding / regulation of embryonic development / MLL1 complex / positive regulation of double-strand break repair via homologous recombination / positive regulation of DNA repair / RNA polymerase II core promoter sequence-specific DNA binding / regulation of DNA repair / Deposition of new CENPA-containing nucleosomes at the centromere / cellular response to estradiol stimulus / TBP-class protein binding / DNA helicase activity / telomere maintenance / Formation of the beta-catenin:TCF transactivating complex / DNA Damage Recognition in GG-NER / negative regulation of canonical Wnt signaling pathway / euchromatin / chromatin DNA binding / ADP binding / nuclear matrix / beta-catenin binding / positive regulation of canonical Wnt signaling pathway / transcription corepressor activity / UCH proteinases / cellular response to UV / nucleosome / unfolded protein binding / protein folding / ATPase binding / HATs acetylate histones / spermatogenesis / DNA helicase / DNA recombination / regulation of apoptotic process / transcription coactivator activity / chromatin remodeling / protein stabilization / regulation of cell cycle / Ub-specific processing proteases / cadherin binding / ribonucleoprotein complex / RNA polymerase II cis-regulatory region sequence-specific DNA binding / cell division / DNA repair / centrosome / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / regulation of DNA-templated transcription / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / ATP hydrolysis activity / extracellular exosome / nucleoplasm / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol Similarity search - Function | ||||||||||||
Biological species | Homo sapiens (human) | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.63 Å | ||||||||||||
Authors | Munoz-Hernandez, H. / Rodriguez, C.F. / Llorca, O. | ||||||||||||
Funding support | Spain, 3items
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Citation | Journal: Sci Adv / Year: 2019 Title: Structural mechanism for regulation of the AAA-ATPases RUVBL1-RUVBL2 in the R2TP co-chaperone revealed by cryo-EM. Authors: Hugo Muñoz-Hernández / Mohinder Pal / Carlos F Rodríguez / Rafael Fernandez-Leiro / Chrisostomos Prodromou / Laurence H Pearl / Oscar Llorca / Abstract: The human R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) is an HSP90 co-chaperone required for the maturation of several essential multiprotein complexes, including RNA polymerase II, small nucleolar ...The human R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) is an HSP90 co-chaperone required for the maturation of several essential multiprotein complexes, including RNA polymerase II, small nucleolar ribonucleoproteins, and PIKK complexes such as mTORC1 and ATR-ATRIP. RUVBL1-RUVBL2 AAA-ATPases are also primary components of other essential complexes such as INO80 and Tip60 remodelers. Despite recent efforts, the molecular mechanisms regulating RUVBL1-RUVBL2 in these complexes remain elusive. Here, we report cryo-EM structures of R2TP and show how access to the nucleotide-binding site of RUVBL2 is coupled to binding of the client recruitment component of R2TP (PIH1D1) to its DII domain. This interaction induces conformational rearrangements that lead to the destabilization of an N-terminal segment of RUVBL2 that acts as a gatekeeper to nucleotide exchange. This mechanism couples protein-induced motions of the DII domains with accessibility of the nucleotide-binding site in RUVBL1-RUVBL2, and it is likely a general mechanism shared with other RUVBL1-RUVBL2-containing complexes. | ||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6qi9.cif.gz | 336.4 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6qi9.ent.gz | 270.1 KB | Display | PDB format |
PDBx/mmJSON format | 6qi9.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6qi9_validation.pdf.gz | 1.1 MB | Display | wwPDB validaton report |
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Full document | 6qi9_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 6qi9_validation.xml.gz | 56.3 KB | Display | |
Data in CIF | 6qi9_validation.cif.gz | 83.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/qi/6qi9 ftp://data.pdbj.org/pub/pdb/validation_reports/qi/6qi9 | HTTPS FTP |
-Related structure data
Related structure data | 4553MC 4552C 4554C 4555C 4556C 4557C 6qi8C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | 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: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9Y265, DNA helicase #2: Protein | 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: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q9Y230, DNA helicase #3: Chemical | ChemComp-ADP / |
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-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: RUVBL1-RUVBL2 in an open conformation (ADP-empty) / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Experimental value: NO |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Escherichia coli BL21(DE3) (bacteria) |
Buffer solution | pH: 7.8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 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 |
Image recording | Electron dose: 1.18 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.14_3260: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 408781 | ||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 4.63 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 33466 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 6FO1 Accession code: 6FO1 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||
Refine LS restraints |
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