Protein Family Models

The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. The BRCT domain of XRCC1 forms a homodimer in the crystal structure. This suggests that pairs of BRCT domains associate as homo- or heterodimers. BRCT domains are often found as tandem-repeat pairs [2]. Structures of the BRCA1 BRCT domains revealed a basis for a widely utilised head-to-tail BRCT-BRCT oligomerisation mode [3]. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. Disease associated missense and nonsense mutations in the BRCA1 BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants [5]. Original discovery of duplicated domain in BRCA1. [1]. 8673121. BRCA1 protein products ...Functional motifs... Koonin EV, Altschul SF, Bork P;. Nature Genet 1996;13:266-268. Extension of BRCT superfamily. [2]. 15501676. Interactions between BRCT repeats and phosphoproteins: tangled up in two. Glover JN, Williams RS, Lee MS;. Trends Biochem Sci. 2004;29:579-585. [3]. 11573086. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Williams RS, Green R, Glover JN;. Nat Struct Biol. 2001;8:838-842. [4]. 15133503. Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. Williams RS, Lee MS, Hau DD, Glover JN;. Nat Struct Mol Biol. 2004;11:519-525. [5]. 14534301. Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. Williams. TRUNCATED at 1650 bytes (from Pfam)

Date:

2024-10-16