1t15
From Proteopedia
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'''Crystal Structure of the Brca1 BRCT Domains in Complex with the Phosphorylated Interacting Region from Bach1 Helicase''' | '''Crystal Structure of the Brca1 BRCT Domains in Complex with the Phosphorylated Interacting Region from Bach1 Helicase''' | ||
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[[Category: Smerdon, S J.]] | [[Category: Smerdon, S J.]] | ||
[[Category: Yaffe, M B.]] | [[Category: Yaffe, M B.]] | ||
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Revision as of 06:22, 3 May 2008
Crystal Structure of the Brca1 BRCT Domains in Complex with the Phosphorylated Interacting Region from Bach1 Helicase
Contents |
Overview
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.
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
1T15 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer., Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ, Nat Struct Mol Biol. 2004 Jun;11(6):512-8. Epub 2004 May 9. PMID:15133502 Page seeded by OCA on Sat May 3 09:22:37 2008
