The complete structure of the human TFIIH core complex

Elife. 2019 Mar 12;8:e44771. doi: 10.7554/eLife.44771.


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.

Keywords: DNA repair; Helicase; Macromolecular complex; Transcription; cryo-electron microscopy; human; molecular biophysics; structural biology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / chemistry
  • Cryoelectron Microscopy
  • DNA Damage
  • DNA Helicases / chemistry*
  • DNA Helicases / metabolism
  • DNA Repair
  • DNA-Binding Proteins / chemistry*
  • HeLa Cells
  • Humans
  • Mutation
  • NF-kappa B p52 Subunit / chemistry*
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • RNA-Binding Proteins / chemistry
  • Transcription Factor TFIIH / chemistry*
  • Transcription Factor TFIIH / genetics
  • Transcription Factor TFIIH / physiology*
  • Transcription Factors / chemistry
  • Transcription, Genetic
  • Xeroderma Pigmentosum Group D Protein / chemistry


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • MNAT1 protein, human
  • NF-kappa B p52 Subunit
  • P62 protein, human
  • RNA-Binding Proteins
  • Transcription Factors
  • WDR77 protein, human
  • XPBC-ERCC-3 protein
  • Transcription Factor TFIIH
  • DNA Helicases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human

Associated data

  • PDB/6NMI