Document Detail

Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.
MedLine Citation:
PMID:  15125843     Owner:  NLM     Status:  MEDLINE    
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.
Eric N Shiozaki; Lichuan Gu; Nieng Yan; Yigong Shi
Related Documents :
24059223 - Pharmacophore-based 3d qsar and molecular docking studies to identify new non-peptidic ...
18776303 - Structural stability analysis of the intermediates in the folding pathway of human telo...
6178553 - The mechanism of peptidergic miosis. i. the structural basis of miotic potency among bi...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular cell     Volume:  14     ISSN:  1097-2765     ISO Abbreviation:  Mol. Cell     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-05     Completed Date:  2004-06-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  405-12     Citation Subset:  IM    
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ 08544, USA.
Data Bank Information
Bank Name/Acc. No.:
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
BRCA1 Protein / 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
Macromolecular Substances
Models, Molecular
Molecular Sequence Data
Mutation, Missense / genetics
Peptides / chemistry,  genetics,  metabolism
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
Reg. No./Substance:
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

Previous Document:  The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibi...
Next Document:  Effect of bracing on the quality of life of adolescents with idiopathic scoliosis.