1T2V

Structural basis of phospho-peptide recognition by the BRCT domain of BRCA1, structure with phosphopeptide

Summary for 1T2V

• Entry DOI: 10.2210/pdb1t2v/pdb
• Related: 1JNX 1N5O 1T2U
• Descriptor: Breast cancer type 1 susceptibility protein, BRCTide-7PS (2 entities in total)
• Functional Keywords: brct, brca1, breast cancer, cell signaling, missense mutation, phosphopeptide, antitumor protein
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus. Isoform 3: Cytoplasm. Isoform 5: Cytoplasm: P38398
• Total number of polymer chains: 10
• Total formula weight: 131921.36

Authors

Williams, R.S.,Lee, M.S.,Hau, D.D.,Glover, J.N.M. (deposition date: 2004-04-22, release date: 2004-05-11, Last modification date: 2024-10-30)

Primary citation

Williams, R.S.,Lee, M.S.,Hau, D.D.,Glover, J.N.M.
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1
Nat.Struct.Mol.Biol., 11:519-525, 2004

PubMed Abstract: The BRCT repeats in BRCA1 are essential for its tumor suppressor activity and interact with phosphorylated protein targets containing the sequence pSer-X-X-Phe, where X indicates any residue. The structure of the tandem BRCA1 BRCT repeats bound to an optimized phosphopeptide reveals that the N-terminal repeat harbors a conserved BRCT phosphoserine-binding pocket, while the interface between the repeats forms a hydrophobic groove that recognizes the phenylalanine. Crystallographic and biochemical data suggest that the structural integrity of both binding sites is essential for peptide recognition. The diminished peptide-binding capacity observed for cancer-associated BRCA1-BRCT variants may explain the enhanced cancer risks associated with these mutations.

PubMed: 15133503
DOI: 10.1038/nsmb776

Experimental method

X-RAY DIFFRACTION (3.3 Å)