Structure of the DNA repair helicase XPD

Cell. 2008 May 30;133(5):801-12. doi: 10.1016/j.cell.2008.04.029.


The XPD helicase (Rad3 in Saccharomyces cerevisiae) is a component of transcription factor IIH (TFIIH), which functions in transcription initiation and Nucleotide Excision Repair in eukaryotes, catalyzing DNA duplex opening localized to the transcription start site or site of DNA damage, respectively. XPD has a 5' to 3' polarity and the helicase activity is dependent on an iron-sulfur cluster binding domain, a feature that is conserved in related helicases such as FancJ. The xpd gene is the target of mutation in patients with xeroderma pigmentosum, trichothiodystrophy, and Cockayne's syndrome, characterized by a wide spectrum of symptoms ranging from cancer susceptibility to neurological and developmental defects. The 2.25 A crystal structure of XPD from the crenarchaeon Sulfolobus tokodaii, presented here together with detailed biochemical analyses, allows a molecular understanding of the structural basis for helicase activity and explains the phenotypes of xpd mutations in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / genetics*
  • Archaeal Proteins / metabolism
  • Cockayne Syndrome / genetics
  • Cockayne Syndrome / metabolism
  • Crystallography, X-Ray
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / genetics
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Structural Homology, Protein
  • Sulfolobus / enzymology*
  • Trichothiodystrophy Syndromes / genetics
  • Trichothiodystrophy Syndromes / metabolism
  • Xeroderma Pigmentosum / genetics
  • Xeroderma Pigmentosum / metabolism
  • Xeroderma Pigmentosum Group D Protein / chemistry*
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Xeroderma Pigmentosum Group D Protein / metabolism


  • Archaeal Proteins
  • Iron-Sulfur Proteins
  • Xeroderma Pigmentosum Group D Protein

Associated data

  • PDB/2VL7