2kn7 | pdb_00002kn7
Structure of the XPF-single strand DNA complex
Structural highlights
Disease[XPF_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] Function[XPF_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 PubMedHuman XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged DNA strand at the 5' end during nucleotide excision repair. We determined the structure of the complex of the C-terminal domain of XPF with 10 nt ssDNA. A positively charged region within the second helix of the first HhH motif contacts the ssDNA phosphate backbone. One guanine base is flipped out of register and positioned in a pocket contacting residues from both HhH motifs of XPF. Comparison to other HhH-containing proteins indicates a one-residue deletion in the second HhH motif of XPF that has altered the hairpin conformation, thereby permitting ssDNA interactions. Previous nuclear magnetic resonance studies showed that ERCC1 in the XPF-ERCC1 heterodimer can bind dsDNA. Combining the two observations gives a model that underscores the asymmetry of the human XPF/ERCC1 heterodimer in binding at an ss/ds DNA junction. The structure of the XPF-ssDNA complex underscores the distinct roles of the XPF and ERCC1 helix- hairpin-helix domains in ss/ds DNA recognition.,Das D, Folkers GE, van Dijk M, Jaspers NG, Hoeijmakers JH, Kaptein R, Boelens R Structure. 2012 Apr 4;20(4):667-75. Epub 2012 Apr 3. PMID:22483113[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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