Structure of the DNA repair helicase XPD.
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.
Centre for Biomolecular Sciences, University of St. Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK.
Huanting
H
Liu
Jana
J
Rudolf
Kenneth A
KA
Johnson
Stephen A
SA
McMahon
Muse
M
Oke
Lester
L
Carter
Anne-Marie
AM
McRobbie
Sara E
SE
Brown
James H
JH
Naismith
Malcolm F
MF
White
D019943:Amino Acid Substitution; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D016944:Sulfolobus / Q000201:enzymology*; D054463:Trichothiodystrophy Syndromes / Q000235:genetics / Q000378:metabolism; D014983:Xeroderma Pigmentosum / Q000235:genetics / Q000378:metabolism; D051759:Xeroderma Pigmentosum Group D Protein / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D019843:Archaeal Proteins; D007506:Iron-Sulfur Proteins; D051759:Xeroderma Pigmentosum Group D Protein