2MUT

Solution structure of the F231L mutant ERCC1-XPF dimerization region

Summary for 2MUT

• Entry DOI: 10.2210/pdb2mut/pdb
• NMR Information: BMRB: 25232
• Descriptor: DNA excision repair protein ERCC-1, DNA repair endonuclease XPF (2 entities in total)
• Functional Keywords: ercc1-xpf, f231l, nucleotide excision repair, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Nucleus. Isoform 2: Cytoplasm. Isoform 3: Nucleus. Isoform 4: Nucleus: P07992; Nucleus : Q92889
• Total number of polymer chains: 2
• Total formula weight: 20216.19

Authors

Faridounnia, M.,Wienk, H.,Kovacic, L.,Folkers, G.E.,Jaspers, N.G.J.,Kaptein, R.,Hoeijmakers, J.H.J.,Boelens, R. (deposition date: 2014-09-17, release date: 2015-06-24, Last modification date: 2024-05-15)

Primary citation

Faridounnia, M.,Wienk, H.,Kovacic, L.,Folkers, G.E.,Jaspers, N.G.,Kaptein, R.,Hoeijmakers, J.H.,Boelens, R.
The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex.
J.Biol.Chem., 290:20541-20555, 2015

PubMed Abstract: The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe(231), Leu(231) lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation.

PubMed: 26085086
DOI: 10.1074/jbc.M114.635169

Experimental method

SOLUTION NMR