The complete structure of the human TFIIH core complex.
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Transcription factor IIH (TFIIH) is a heterodecameric protein complex critical for transcription initiation by RNA polymerase II and nucleotide excision DNA repair. The TFIIH core complex is sufficient for its repair functions and harbors the XPB and XPD DNA-dependent ATPase/helicase subunits, which are affected by human disease mutations. Transcription initiation additionally requires the CdK activating kinase subcomplex. Previous structural work has provided only partial insight into the architecture of TFIIH and its interactions within transcription pre-initiation complexes. Here, we present the complete structure of the human TFIIH core complex, determined by phase-plate cryo-electron microscopy at 3.7 Å resolution. The structure uncovers the molecular basis of TFIIH assembly, revealing how the recruitment of XPB by p52 depends on a pseudo-symmetric dimer of homologous domains in these two proteins. The structure also suggests a function for p62 in the regulation of XPD, and allows the mapping of previously unresolved human disease mutations.
Cell Cycle Proteins
Transcription Factor TFIIH
Xeroderma Pigmentosum Group D Protein
NF-kappa B p52 Subunit
License start date
eLife, 2019, 8
ELIFE SCIENCES PUBLICATIONS LTD
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by/4.0
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