1T15

Crystal Structure of the Brca1 BRCT Domains in Complex with the Phosphorylated Interacting Region from Bach1 Helicase

Summary for 1T15

• Entry DOI: 10.2210/pdb1t15/pdb
• Descriptor: Breast cancer type 1 susceptibility protein, BRCA1 interacting protein C-terminal helicase 1 (3 entities in total)
• Functional Keywords: protein-peptide complex, antitumor protein
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus. Isoform 3: Cytoplasm. Isoform 5: Cytoplasm: P38398
• Total number of polymer chains: 2
• Total formula weight: 25493.16

Authors

Clapperton, J.A.,Manke, I.A.,Lowery, D.M.,Ho, T.,Haire, L.F.,Yaffe, M.B.,Smerdon, S.J. (deposition date: 2004-04-15, release date: 2004-05-11, Last modification date: 2024-10-30)

Primary citation

Clapperton, J.A.,Manke, I.A.,Lowery, D.M.,Ho, T.,Haire, L.F.,Yaffe, M.B.,Smerdon, S.J.
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer
Nat.Struct.Mol.Biol., 11:512-518, 2004

PubMed Abstract: Germline mutations in the BRCA1 tumor suppressor gene often result in a significant increase in susceptibility to breast and ovarian cancers. Although the molecular basis of their effects remains largely obscure, many mutations are known to target the highly conserved C-terminal BRCT repeats that function as a phosphoserine/phosphothreonine-binding module. We report the X-ray crystal structure at a resolution of 1.85 A of the BRCA1 tandem BRCT domains in complex with a phosphorylated peptide representing the minimal interacting region of the DEAH-box helicase BACH1. The structure reveals the determinants of this novel class of BRCA1 binding events. We show that a subset of disease-linked mutations act through specific disruption of phospho-dependent BRCA1 interactions rather than through gross structural perturbation of the tandem BRCT domains.

PubMed: 15133502
DOI: 10.1038/nsmb775

Experimental method

X-RAY DIFFRACTION (1.85 Å)