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Structure of an XRCC1 BRCT domain: a new protein–protein interaction module
Author(s) -
Zhang Xiaodong,
Moréra Solange,
Bates Paul A.,
Whitehead Philip C.,
Coffer Arnold I.,
Hainbucher Karl,
Nash Rachel A.,
Sternberg Michael J.E.,
Lindahl Tomas,
Freemont Paul S.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.21.6404
Subject(s) - biology , xrcc1 , domain (mathematical analysis) , computational biology , protein domain , protein structure , protein–protein interaction , genetics , gene , biochemistry , genotype , single nucleotide polymorphism , mathematical analysis , mathematics
The BRCT domain ( BR CA1 C ‐ t erminus), first identified in the breast cancer suppressor protein BRCA1, is an evolutionarily conserved protein–protein interaction region of ∼95 amino acids found in a large number of proteins involved in DNA repair, recombination and cell cycle control. Here we describe the first three‐dimensional structure and fold of a BRCT domain determined by X‐ray crystallography at 3.2 Å resolution. The structure has been obtained from the C‐terminal region of the human DNA repair protein XRCC1, and comprises a four‐stranded parallel β‐sheet surrounded by three α‐helices, which form an autonomously folded domain. The compact XRCC1 structure explains the observed sequence homology between different BRCT motifs and provides a framework for modelling other BRCT domains. Furthermore, the established structure of an XRCC1 BRCT homodimer suggests potential protein–protein interaction sites for the complementary BRCT domain in DNA ligase III, since these two domains form a stable heterodimeric complex. Based on the XRCC1 BRCT structure, we have constructed a model for the C‐terminal BRCT domain of BRCA1, which frequently is mutated in familial breast and ovarian cancer. The model allows insights into the effects of such mutations on the fold of the BRCT domain.