4Y18: Structure Of Brca1 Brct Domains In Complex With Abraxas Double Phosphorylated Peptide

Citation:
Abstract
BRCA1 accumulation at DNA damage sites is an important step for its function in the DNA damage response and in DNA repair. BRCA1-BRCT domains bind to proteins containing the phosphorylated serine-proline-x-phenylalanine (pSPxF) motif including Abraxas, Bach1/FancJ, and CtIP. In this study, we demonstrate that ionizing radiation (IR)-induces ATM-dependent phosphorylation of serine 404 (S404) next to the pSPxF motif. Crystal structures of BRCT/Abraxas show that phosphorylation of S404 is important for extensive interactions through the N-terminal sequence outside the pSPxF motif and leads to formation of a stable dimer. Mutation of S404 leads to deficiency in BRCA1 accumulation at DNA damage sites and cellular sensitivity to IR. In addition, two germline mutations of BRCA1 are found to disrupt the dimer interface and dimer formation. Thus, we demonstrate a mechanism involving IR-induced phosphorylation and dimerization of the BRCT/Abraxas complex for regulating Abraxas-mediated recruitment of BRCA1 in response to IR.
PDB ID: 4Y18Download
MMDB ID: 135965
PDB Deposition Date: 2015/2/6
Updated in MMDB: 2016/02
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4Y18: dimeric; determined by author and by software (PISA)
Molecular Components in 4Y18
Label Count Molecule
Proteins (2 molecules)
1
Breast Cancer Type 1 Susceptibility Protein(Gene symbol: BRCA1)
Molecule annotation
1
Brca1-a Complex Subunit Abraxas(Gene symbol: ABRAXAS1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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