InterPro domain: IPR042493

XPD is divided into four domains. The first three domains together with alpha-helix 22 from domain 4 form a donut-shaped structure containing a hole [ 1 ]. Domains 1 and 4 represent the RecA-like fold that is present in all helicases of superfamilies 1 and 2 (SF1 and SF2) [ 2 ]. Domains 2 and 3 are insertions, which emerge from domain 1. Domain 2 displays an exclusively alpha-helical architecture consisting of six alpha-helices and one 3-10 helix that surround the central 4Fe4S cluster. The FeS cluster is coordinated by four cysteines, consistent with the coordination typically observed in 4Fe4S clusters [ 3 ]. The FeS domain is vital for its helicase activity and might be involved in the damage recognition process [ 3 , 4 , 5 , 5 ].

This entry represents the FeS cluster domain found in XPD family members that are mostly from bacteria and archaea.

XPD belongs to a family of ATP-dependent helicases that are characterised by a 'D-E-A-H' motif [ 6 ]. This resembles the 'D-E-A-D-box' of other known helicases, which represents a special version of the B motif of ATP-binding proteins. In XPD, His replaces the second Asp.

1. Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biol. 6, e149
2. Structure and mechanism of helicases and nucleic acid translocases. Annu. Rev. Biochem. 76, 23-50
3. XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. Cell 133, 789-800
4. Structure of the DNA repair helicase XPD. Cell 133, 801-12
5. The DNA repair helicases XPD and FancJ have essential iron-sulfur domains. Mol. Cell 23, 801-8
6. The RAD3 gene is a member of the DEAH family RNA helicase-like protein. Nucleic Acids Res. 19, 6331