1t2u | pdb_00001t2u
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1: structure of BRCA1 missense variant V1809F
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| 1t2u, resolution 2.80Å | |||||||||||||
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| Ligands: | CO, SO4 | ||||||||||||
| Gene: | BRCA1 (Homo sapiens) | ||||||||||||
| Related: | 1JNX, 1N5O, 1T2V
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
Disease
Known disease associated with this structure: Breast cancer-1 OMIM:[113705], Breast-ovarian cancer OMIM:[113705], Ovarian cancer OMIM:[113705], Papillary serous carcinoma of the peritoneum OMIM:[113705]
About this Structure
1T2U is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1., Williams RS, Lee MS, Hau DD, Glover JN, Nat Struct Mol Biol. 2004 Jun;11(6):519-25. Epub 2004 May 9. PMID:15133503
Page seeded by OCA on Sun Mar 30 23:50:27 2008
