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- PDB-6zy8: Cryo-EM structure of the entire Human topoisomerase II alpha in S... -
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Basic information
Entry | Database: PDB / ID: 6zy8 | ||||||||||||
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Title | Cryo-EM structure of the entire Human topoisomerase II alpha in State 2 | ||||||||||||
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Function / homology | ![]() negative regulation of DNA duplex unwinding / positive regulation of single stranded viral RNA replication via double stranded DNA intermediate / sister chromatid segregation / apoptotic chromosome condensation / resolution of meiotic recombination intermediates / female meiotic nuclear division / DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) complex / embryonic cleavage / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||
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Method | ![]() ![]() ![]() | ||||||||||||
![]() | Vanden Broeck, A. / Lamour, V. | ||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for allosteric regulation of Human Topoisomerase IIα. Authors: Arnaud Vanden Broeck / Christophe Lotz / Robert Drillien / Léa Haas / Claire Bedez / Valérie Lamour / ![]() Abstract: The human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in ...The human type IIA topoisomerases (Top2) are essential enzymes that regulate DNA topology and chromosome organization. The Topo IIα isoform is a prime target for antineoplastic compounds used in cancer therapy that form ternary cleavage complexes with the DNA. Despite extensive studies, structural information on this large dimeric assembly is limited to the catalytic domains, hindering the exploration of allosteric mechanism governing the enzyme activities and the contribution of its non-conserved C-terminal domain (CTD). Herein we present cryo-EM structures of the entire human Topo IIα nucleoprotein complex in different conformations solved at subnanometer resolutions (3.6-7.4 Å). Our data unveils the molecular determinants that fine tune the allosteric connections between the ATPase domain and the DNA binding/cleavage domain. Strikingly, the reconstruction of the DNA-binding/cleavage domain uncovers a linker leading to the CTD, which plays a critical role in modulating the enzyme's activities and opens perspective for the analysis of post-translational modifications. | ||||||||||||
History |
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Structure visualization
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 460.7 KB | Display | ![]() |
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PDB format | ![]() | 358.7 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 11554MC ![]() 6zy5C ![]() 6zy6C ![]() 6zy7C M: map data used to model this data C: citing same article ( |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 174654.406 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() References: UniProt: P11388, ![]() #2: DNA chain | Mass: 5099.298 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() #3: DNA chain | Mass: 4080.671 Da / Num. of mol.: 2 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() #4: Chemical | #5: Chemical | ![]() Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
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Molecular weight | Value: 0.295 MDa / Experimental value: NO | ||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 8 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() | ||||||||||||||||||||||||
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 95 % / Chamber temperature: 283 K |
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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![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 50 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
EM imaging optics | Energyfilter name![]() |
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Processing
Software | Name: PHENIX / Version: 1.18rc4_3812: / 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: 1908092 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 7.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 13420 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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Refine LS restraints |
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