BRCT Domain
Class:Phospho-Ser binding
Structure:

No Image The BRCT domain consists of repeats containing approximately ~90-100 amino acids. Each BRCT repeat adopts a characteristic fold with a central, parallel four-stranded β-sheet, along with a pair of α-helices packed against one face and a single α-helix packed against the opposite face of the sheet. The arrangement of the α1, α3 and the central β-sheet is conserved in all repeats as a number of key hydrophobic residues maintain the packing of the BRCT fold. The two BRCT repeats in BRCA1 interact in a head-to-tail manner. In this arrangement, the N-terminal half of the one BRCT domain forms a pocket for pSer as the C-terminal half of the same domain generates a hydrophobic pocket for Phe.
Structure Reference:
Shiozaki, E. N. et al. (2004) Mol. Cell. 14(3), 405-412. PDB: 1T29.
Clapperton, J.A. et al. (2004) Nature Struct. Biol. 11(6), 512-518.
SWilliams, R. S. et al. (2004) Nature Struct. Biol. 11(6), 519-525.
Domain binding and function:
The BRCT (BRCA1 C-terminal) domain was first identified by sequence analysis of the C-terminus of the BRCA1 gene which contained a pair of repeats found mutated by truncation or loss in cancers, indicating its function to be essential for the tumor suppressor function of BRCA1.  The BRCT domain consists of ~90-100 amino acid residues arranged into a central β-sheet surrounded by 2-3 α-helices. While single BRCT repeats have been found (e.g. XRCC1 and DNA ligase III), most BRCT repeats that have been detected occur in multiples.   Functionally, BRCT containing proteins are involved in DNA repair, the DNA damage response and cell cycle regulation, most importantly by directing protein-protein interactions.  In a number of cases, tandem BRCT repeats constitute a phosphopeptide binding domain with ligand specificity encoded in residues C-terminal to the critical phospho-serine. Phosphopeptide binding occurs in a groove that involves both the N- and C-terminal repeats and exhibits specificity for phospho-serine containing peptides.  
Examples of Proteins: 
BRCT domain protein
Binding partners Phosphopeptide ligands
BRCA1 BACH1, p53, CtIP, HDACs, CBP pSer-X-X-Phe
XRCC1

LigIIIα

XRCC4 DNA Ligase IV
TOPBP1 E2F1
53BP1 p53
RAD9 RAD4 pSer-[YILQP]-I-I
BARD
pSer-[DE]-[DE]-E
MDC1/NFBD1 H2AX
Ser-Ω-[EVDI]-Ω




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