| Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling. | |
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MedLine Citation:
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PMID: 15125843 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The recognition of the phosphorylated BACH1 helicase by the BRCA1 C-terminal (BRCT) repeats is important to the tumor suppressor function of BRCA1. Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution. The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats. This surface cleft is highly conserved in BRCA1 across species, suggesting an evolutionarily conserved function of phosphopeptide recognition. Importantly, conserved amino acids critical for BACH1 binding are frequently targeted for missense mutations in breast cancer. These mutations greatly diminish the ability of BRCA1 to interact with the phosphorylated BACH1 peptide. Additional structural analysis revealed significant implications for understanding the function of the BRCT family of proteins in DNA damage and repair signaling. |
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Authors:
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Eric N Shiozaki; Lichuan Gu; Nieng Yan; Yigong Shi |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Molecular cell Volume: 14 ISSN: 1097-2765 ISO Abbreviation: Mol. Cell Publication Date: 2004 May |
Date Detail:
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Created Date: 2004-05-05 Completed Date: 2004-06-23 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9802571 Medline TA: Mol Cell Country: United States |
Other Details:
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Languages: eng Pagination: 405-12 Citation Subset: IM |
Affiliation:
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Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/1T29 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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BRCA1 Protein
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chemistry*,
genetics,
metabolism Basic-Leucine Zipper Transcription Factors Binding Sites / physiology Breast Neoplasms / genetics* Carcinoma / genetics* Conserved Sequence Crystallography, X-Ray Fanconi Anemia Complementation Group Proteins Female Humans Macromolecular Substances Models, Molecular Molecular Sequence Data Mutation, Missense / genetics Peptides / chemistry, genetics, metabolism Phosphorylation Protein Binding / physiology Protein Conformation Protein Structure, Tertiary / physiology Repetitive Sequences, Amino Acid / physiology* Sequence Homology, Amino Acid Signal Transduction / physiology Transcription Factors / chemistry*, metabolism Tumor Suppressor Proteins / chemistry*, genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/BACH1 protein, human; 0/BRCA1 Protein; 0/Basic-Leucine Zipper Transcription Factors; 0/Fanconi Anemia Complementation Group Proteins; 0/Macromolecular Substances; 0/Peptides; 0/Transcription Factors; 0/Tumor Suppressor Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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