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TitleThe cryo-electron microscopy structure of human transcription factor IIH.
Journal, issue, pagesNature, Vol. 549, Issue 7672, Page 414-417, Year 2017
Publish dateSep 21, 2017
AuthorsBasil J Greber / Thi Hoang Duong Nguyen / Jie Fang / Pavel V Afonine / Paul D Adams / Eva Nogales /
PubMed AbstractHuman transcription factor IIH (TFIIH) is part of the general transcriptional machinery required by RNA polymerase II for the initiation of eukaryotic gene transcription. Composed of ten subunits ...Human transcription factor IIH (TFIIH) is part of the general transcriptional machinery required by RNA polymerase II for the initiation of eukaryotic gene transcription. Composed of ten subunits that add up to a molecular mass of about 500 kDa, TFIIH is also essential for nucleotide excision repair. The seven-subunit TFIIH core complex formed by XPB, XPD, p62, p52, p44, p34, and p8 is competent for DNA repair, while the CDK-activating kinase subcomplex, which includes the kinase activity of CDK7 as well as the cyclin H and MAT1 subunits, is additionally required for transcription initiation. Mutations in the TFIIH subunits XPB, XPD, and p8 lead to severe premature ageing and cancer propensity in the genetic diseases xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy, highlighting the importance of TFIIH for cellular physiology. Here we present the cryo-electron microscopy structure of human TFIIH at 4.4 Å resolution. The structure reveals the molecular architecture of the TFIIH core complex, the detailed structures of its constituent XPB and XPD ATPases, and how the core and kinase subcomplexes of TFIIH are connected. Additionally, our structure provides insight into the conformational dynamics of TFIIH and the regulation of its activity.
External linksNature / PubMed:28902838 / PubMed Central
MethodsEM (single particle)
Resolution4.4 - 5.4 Å
Structure data

EMDB-3802, PDB-5of4:
The cryo-EM structure of human TFIIH
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-8816:
TFIIH reconstruction from particles sorted for density near the XPD ARCH domain using signal-subtracted classification.
Method: EM (single particle) / Resolution: 5.4 Å

EMDB-8817:
TFIIH reconstruction from particles sorted for the XPD FeS-cluster domain using signal-subtracted classification.
Method: EM (single particle) / Resolution: 4.4 Å

Chemicals

ChemComp-SF4:
IRON/SULFUR CLUSTER / Iron–sulfur cluster

Source
  • homo sapiens (human)
  • Human (human)
KeywordsTRANSCRIPTION / transcription initiation / DNA repair / multiprotein complex / kinase / helicase

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