2aq0 | pdb_00002aq0
Solution structure of the human homodimeric dna repair protein XPF
Structural highlights
DiseaseXPF_HUMAN Defects in ERCC4 are the cause of xeroderma pigmentosum complementation group F (XP-F) [MIM:278760; also known as xeroderma pigmentosum VI (XP6). XP-F is an autosomal recessive disease characterized by hypersensitivity of the skin to sunlight followed by high incidence of skin cancer and frequent neurologic abnormalities.[1] [2] [3] Defects in ERCC4 are a cause of XFE progeroid syndrome (XFEPS) [MIM:610965. This syndrome is illustrated by one patient who presented with dwarfism, cachexia and microcephaly.[4] FunctionXPF_HUMAN Structure-specific DNA repair endonuclease responsible for the 5-prime incision during DNA repair. Involved in homologous recombination that assists in removing interstrand cross-link.[5] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe human XPF-ERCC1 protein complex plays an essential role in nucleotide excision repair by catalysing positioned nicking of a DNA strand at the 5' side of the damage. We have recently solved the structure of the heterodimeric complex of the C-terminal domains of XPF and ERCC1 (Tripsianes et al., Structure 2005;13:1849-1858). We found that this complex comprises a pseudo twofold symmetry axis and that the helix-hairpin-helix motif of ERCC1 is required for DNA binding, whereas the corresponding domain of XPF is functioning as a scaffold for complex formation with ERCC1. Despite the functional importance of heterodimerization, the C-terminal domain of XPF can also form homodimers in vitro. We here compare the stabilities of homodimeric and heterodimeric complexes of the C-terminal domains of XPF and ERCC1. The higher stability of the XPF HhH complexes under various experimental conditions, determined using CD and NMR spectroscopy and mass spectrometry, is well explained by the structural differences that exist between the HhH domains of the two complexes. The XPF HhH homodimer has a larger interaction interface, aromatic stacking interactions, and additional hydrogen bond contacts as compared to the XPF/ERCC1 HhH complex, which accounts for its higher stability. The HhH domain of the human DNA repair protein XPF forms stable homodimers.,Das D, Tripsianes K, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R, Folkers GE Proteins. 2008 Mar;70(4):1551-63. PMID:17912758[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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