Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains

Maria Victoria E Botuyan, Yves Nominé, Xiaochun Yu, Nenad Juranic, Slobodan I Macura, Junjie Chen, Georges Mer

Research output: Contribution to journalArticle

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Abstract

BRCT tandem domains, found in many proteins involved in DNA damage checkpoint and DNA repair pathways, were recently shown to be phosphopeptide binding motifs. Using solution nuclear magnetic resonance (NMR) spectroscopy and mutational analysis, we have characterized the interaction of BRCA1-BRCT domains with a phosphoserine-containing peptide derived from the DNA repair helicase BACH1. We show that a phenylalanine in the +3 position from the phosphoserine of BACH1 is bound to a conserved hydrophobic pocket formed between the two BRCT domains and that recognition of the phosphate group is mediated by lysine and serine side chains from the amino-terminal BRCT domain. Mutations that prevent phosphopeptide binding abolish BRCA1 function in DNA damage-induced checkpoint control. Our NMR data also reveal a dynamic interaction between BRCA1-BRCT and BACH1, where the bound phosphopeptide exists as an equilibrium of two conformations and where BRCA1-BRCT undergoes a transition to a more rigid conformation upon peptide binding.

Original languageEnglish (US)
Pages (from-to)1137-1146
Number of pages10
JournalStructure
Volume12
Issue number7
DOIs
StatePublished - Jul 2004

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Phosphopeptides
Phosphoserine
DNA Repair
DNA Damage
Magnetic Resonance Spectroscopy
DNA Helicases
Peptides
Phenylalanine
Serine
Lysine
Phosphates
Mutation
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains. / Botuyan, Maria Victoria E; Nominé, Yves; Yu, Xiaochun; Juranic, Nenad; Macura, Slobodan I; Chen, Junjie; Mer, Georges.

In: Structure, Vol. 12, No. 7, 07.2004, p. 1137-1146.

Research output: Contribution to journalArticle

Botuyan, Maria Victoria E ; Nominé, Yves ; Yu, Xiaochun ; Juranic, Nenad ; Macura, Slobodan I ; Chen, Junjie ; Mer, Georges. / Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains. In: Structure. 2004 ; Vol. 12, No. 7. pp. 1137-1146.
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