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Open data
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Basic information
Entry | Database: PDB / ID: 7ad8 | ||||||
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Title | Core TFIIH-XPA-DNA complex with modelled p62 subunit | ||||||
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![]() | DNA BINDING PROTEIN / DNA repair / transcription factor | ||||||
Function / homology | ![]() nucleotide-excision repair factor 1 complex / nucleotide-excision repair involved in interstrand cross-link repair / nucleotide-excision repair, DNA damage recognition / MMXD complex / core TFIIH complex portion of holo TFIIH complex / Cytosolic iron-sulfur cluster assembly / central nervous system myelin formation / response to auditory stimulus / positive regulation of mitotic recombination / hair cell differentiation ...nucleotide-excision repair factor 1 complex / nucleotide-excision repair involved in interstrand cross-link repair / nucleotide-excision repair, DNA damage recognition / MMXD complex / core TFIIH complex portion of holo TFIIH complex / Cytosolic iron-sulfur cluster assembly / central nervous system myelin formation / response to auditory stimulus / positive regulation of mitotic recombination / hair cell differentiation / hair follicle maturation / nucleotide-excision repair factor 3 complex / nucleotide-excision repair, preincision complex assembly / CAK-ERCC2 complex / UV protection / embryonic cleavage / DNA 5'-3' helicase / G protein-coupled receptor internalization / transcription factor TFIIH core complex / transcription factor TFIIH holo complex / UV-damage excision repair / nuclear thyroid hormone receptor binding / regulation of cyclin-dependent protein serine/threonine kinase activity / RNA Polymerase I Transcription Termination / transcription preinitiation complex / regulation of mitotic cell cycle phase transition / 3'-5' DNA helicase activity / DNA 3'-5' helicase / RNA polymerase II general transcription initiation factor activity / transcription factor TFIID complex / spinal cord development / RNA Pol II CTD phosphorylation and interaction with CE during HIV infection / RNA Pol II CTD phosphorylation and interaction with CE / hematopoietic stem cell proliferation / erythrocyte maturation / Formation of the Early Elongation Complex / Formation of the HIV-1 Early Elongation Complex / mRNA Capping / bone mineralization / HIV Transcription Initiation / RNA Polymerase II HIV Promoter Escape / Transcription of the HIV genome / RNA Polymerase II Promoter Escape / RNA Polymerase II Transcription Pre-Initiation And Promoter Opening / RNA Polymerase II Transcription Initiation / RNA Polymerase II Transcription Initiation And Promoter Clearance / ATPase activator activity / DNA topological change / intrinsic apoptotic signaling pathway by p53 class mediator / RNA Polymerase I Transcription Initiation / protein localization to nucleus / hematopoietic stem cell differentiation / embryonic organ development / Tat-mediated elongation of the HIV-1 transcript / transcription by RNA polymerase I / Formation of HIV-1 elongation complex containing HIV-1 Tat / transcription elongation by RNA polymerase I / Formation of HIV elongation complex in the absence of HIV Tat / transcription-coupled nucleotide-excision repair / DNA helicase activity / response to UV / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / hormone-mediated signaling pathway / RNA Polymerase II Pre-transcription Events / extracellular matrix organization / insulin-like growth factor receptor signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / post-embryonic development / determination of adult lifespan / isomerase activity / nucleotide-excision repair / chromosome segregation / transcription initiation at RNA polymerase II promoter / TP53 Regulates Transcription of DNA Repair Genes / RNA Polymerase I Promoter Escape / transcription elongation by RNA polymerase II / promoter-specific chromatin binding / cellular response to gamma radiation / NoRC negatively regulates rRNA expression / base-excision repair / multicellular organism growth / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / spindle / Formation of Incision Complex in GG-NER / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / sequence-specific double-stranded DNA binding / protein localization / 4 iron, 4 sulfur cluster binding / 5'-3' DNA helicase activity / double-stranded DNA binding / protein-macromolecule adaptor activity / response to oxidative stress / in utero embryonic development / transcription by RNA polymerase II / damaged DNA binding / forked DNA-dependent helicase activity Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||
![]() | Koelmel, W. / Kuper, J. / Kisker, C. | ||||||
Funding support | ![]()
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![]() | ![]() Title: The TFIIH subunits p44/p62 act as a damage sensor during nucleotide excision repair. Authors: Jamie T Barnett / Jochen Kuper / Wolfgang Koelmel / Caroline Kisker / Neil M Kad / ![]() ![]() Abstract: Nucleotide excision repair (NER) in eukaryotes is orchestrated by the core form of the general transcription factor TFIIH, containing the helicases XPB, XPD and five 'structural' subunits, p62, p44, ...Nucleotide excision repair (NER) in eukaryotes is orchestrated by the core form of the general transcription factor TFIIH, containing the helicases XPB, XPD and five 'structural' subunits, p62, p44, p34, p52 and p8. Recent cryo-EM structures show that p62 makes extensive contacts with p44 and in part occupies XPD's DNA binding site. While p44 is known to regulate the helicase activity of XPD during NER, p62 is thought to be purely structural. Here, using helicase and adenosine triphosphatase assays we show that a complex containing p44 and p62 enhances XPD's affinity for dsDNA 3-fold over p44 alone. Remarkably, the relative affinity is further increased to 60-fold by dsDNA damage. Direct binding studies show this preference derives from p44/p62's high affinity (20 nM) for damaged ssDNA. Single molecule imaging of p44/p62 complexes without XPD reveals they bind to and randomly diffuse on DNA, however, in the presence of UV-induced DNA lesions these complexes stall. Combined with the analysis of a recent cryo-EM structure, we suggest that p44/p62 acts as a novel DNA-binding entity that enhances damage recognition in TFIIH. This revises our understanding of TFIIH and prompts investigation into the core subunits for an active role during DNA repair and/or transcription. | ||||||
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 | ![]() | 505.5 KB | Display | ![]() |
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PDB format | ![]() | 390.9 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 808.6 KB | Display | ![]() |
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Full document | ![]() | 823.2 KB | Display | |
Data in XML | ![]() | 67.1 KB | Display | |
Data in CIF | ![]() | 104.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 4970M M: map data used to model this data |
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Similar structure data |
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Links
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Assembly
Deposited unit | ![]()
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Components
-DNA chain , 2 types, 2 molecules JK
#1: DNA chain | Mass: 15036.663 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
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#2: DNA chain | Mass: 15075.698 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) ![]() |
-Protein , 3 types, 3 molecules ABG
#3: Protein | Mass: 89404.734 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#5: Protein | Mass: 87021.078 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#9: Protein | Mass: 31422.053 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-General transcription factor IIH subunit ... , 5 types, 5 molecules FEDCI
#4: Protein | Mass: 8060.362 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#6: Protein | Mass: 34416.008 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#7: Protein | Mass: 44481.996 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#8: Protein | Mass: 52245.156 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#10: Protein | Mass: 62116.492 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Non-polymers , 2 types, 7 molecules 


#11: Chemical | ChemComp-SF4 / |
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#12: Chemical | ChemComp-ZN / |
-Details
Has ligand of interest | N |
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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 |
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Sample preparation
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Molecular weight | Experimental value: NO | ||||||||||||||||||||||||
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Source (recombinant) |
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Buffer solution | pH: 7.5 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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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 |
Image recording | Electron dose: 41 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 227776 / Symmetry type: POINT |