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Nature. 2017 Sep 21;549(7672):414-417. doi: 10.1038/nature23903. Epub 2017 Sep 13.

The cryo-electron microscopy structure of human transcription factor IIH.

Author information

1
California Institute for Quantitative Biology (QB3), University of California, Berkeley, California 94720, USA.
2
Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
3
Miller Institute for Basic Research in Science, University of California, Berkeley, California 94720, USA.
4
Howard Hughes Medical Institute, University of California, Berkeley, California 94720, USA.
5
Department of Bioengineering, University of California, Berkeley, California 94720, USA.
6
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.

Abstract

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.

PMID:
28902838
PMCID:
PMC5844561
DOI:
10.1038/nature23903
[Indexed for MEDLINE]
Free PMC Article

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