Home LiteratureArticle Details
PMID: 15242590 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains.

Structure (London, England : 1993) ·Vol. 12 ·No. 7 ·2004-07-00 ·Pages 1137-46

Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G

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.

MeSH Terms
BRCA1 Protein/chemistry,genetics,metabolism Basic-Leucine Zipper Transcription Factors Binding Sites Carrier Proteins/chemistry,metabolism Culture Media DNA Mutational Analysis Fanconi Anemia Complementation Group Proteins Humans Magnetic Resonance Spectroscopy Mutation Protein Binding Protein Structure, Tertiary Transcription Factors/chemistry,metabolism Tumor Cells, Cultured
Chemicals
BACH1 protein, human BRCA1 Protein Basic-Leucine Zipper Transcription Factors Carrier Proteins Culture Media Fanconi Anemia Complementation Group Proteins Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Botuyan Maria Victoria E
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, 200 First Street S.W., Rochester, MN 55905 USA.
Nominé Yves
Yu Xiaochun
Juranic Nenad
Macura Slobodan
Chen Junjie
Mer Georges
References (48)
48 references, click to expand
  1. Solution structure and dynamics of yeast elongin C in complex with a von Hippel-Lindau peptide.
    J Mol Biol. 2001 Sep 7;312(1):177-86 PMID: 11545595
  2. Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains.
    J Biol Chem. 2003 Dec 26;278(52):52914-8 PMID: 14578343
  3. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage.
    Nat Genet. 2002 Mar;30(3):285-9 PMID: 11836499
  4. Protein backbone angle restraints from searching a database for chemical shift and sequence homology.
    J Biomol NMR. 1999 Mar;13(3):289-302 PMID: 10212987
  5. Comparison of BRCT domains of BRCA1 and 53BP1: a biophysical analysis.
    Protein Sci. 2004 Mar;13(3):617-25 PMID: 14978302
  6. Torsion angle dynamics for NMR structure calculation with the new program DYANA.
    J Mol Biol. 1997 Oct 17;273(1):283-98 PMID: 9367762
  7. NMRPipe: a multidimensional spectral processing system based on UNIX pipes.
    J Biomol NMR. 1995 Nov;6(3):277-93 PMID: 8520220
  8. Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer.
    Nat Struct Mol Biol. 2004 Jun;11(6):512-8 PMID: 15133502
  9. Structural consequences of a cancer-causing BRCA1-BRCT missense mutation.
    J Biol Chem. 2003 Jan 24;278(4):2630-5 PMID: 12427738
  10. Structure of an XRCC1 BRCT domain: a new protein-protein interaction module.
    EMBO J. 1998 Nov 2;17(21):6404-11 PMID: 9799248
  11. A pulsed field gradient isotope-filtered 3D 13C HMQC-NOESY experiment for extracting intermolecular NOE contacts in molecular complexes.
    FEBS Lett. 1994 Aug 15;350(1):87-90 PMID: 8062930
  12. NMR-based screening in drug discovery.
    Q Rev Biophys. 1999 Aug;32(3):211-40 PMID: 11194565
  13. Megabase chromatin domains involved in DNA double-strand breaks in vivo.
    J Cell Biol. 1999 Sep 6;146(5):905-16 PMID: 10477747
  14. Characterisation of the BRCT domains of the breast cancer susceptibility gene product BRCA1.
    J Mol Biol. 2002 Jul 12;320(3):431-42 PMID: 12096901
  15. Local structural changes caused by peptidyl-prolyl cis/trans isomerization in the native state of proteins.
    Biophys Chem. 2002 May 2;96(2-3):203-12 PMID: 12034441
  16. Solution structure and backbone dynamics of the human DNA ligase IIIalpha BRCT domain.
    Biochemistry. 2001 Nov 6;40(44):13158-66 PMID: 11683624
  17. SUVi and BACH1: a new subfamily of mammalian helicases?
    Mutat Res. 2001 Nov 1;487(1-2):67-71 PMID: 11595410
  18. MOLMOL: a program for display and analysis of macromolecular structures.
    J Mol Graph. 1996 Feb;14(1):51-5, 29-32 PMID: 8744573
  19. A sensitive and robust method for obtaining intermolecular NOEs between side chains in large protein complexes.
    J Biomol NMR. 2003 Mar;25(3):235-42 PMID: 12652135
  20. BRCT repeats as phosphopeptide-binding modules involved in protein targeting.
    Science. 2003 Oct 24;302(5645):636-9 PMID: 14576432
  21. WW domains.
    Structure. 1996 May 15;4(5):495-9 PMID: 8736547
  22. BRCA1 mutations in primary breast and ovarian carcinomas.
    Science. 1994 Oct 7;266(5182):120-2 PMID: 7939630
  23. Partial NMR assignments and secondary structure mapping of the isolated alpha subunit of Escherichia coli tryptophan synthase, a 29-kD TIM barrel protein.
    Protein Sci. 2003 Jan;12(1):185-91 PMID: 12493842
  24. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.
    Science. 1994 Oct 7;266(5182):66-71 PMID: 7545954
  25. The 13C chemical-shift index: a simple method for the identification of protein secondary structure using 13C chemical-shift data.
    J Biomol NMR. 1994 Mar;4(2):171-80 PMID: 8019132
  26. The role of dynamics in allosteric regulation.
    Curr Opin Struct Biol. 2003 Dec;13(6):748-57 PMID: 14675554
  27. Cell signaling. The BRCT domain: signaling with friends?
    Science. 2003 Oct 24;302(5645):579-80 PMID: 14576410
  28. A common sense approach to peak picking in two-, three-, and four-dimensional spectra using automatic computer analysis of contour diagrams. 1991.
    J Magn Reson. 2011 Dec;213(2):357-63 PMID: 22152355
  29. Genetic tools for selective labeling of proteins with alpha-15N-amino acids.
    J Biomol NMR. 1996 Sep;8(2):184-92 PMID: 8914274
  30. NMR View: A computer program for the visualization and analysis of NMR data.
    J Biomol NMR. 1994 Sep;4(5):603-14 PMID: 22911360
  31. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins.
    Science. 1991 May 3;252(5006):668-74 PMID: 1708916
  32. BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function.
    Cell. 2001 Apr 6;105(1):149-60 PMID: 11301010
  33. Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling.
    Mol Cell. 2004 May 7;14(3):405-12 PMID: 15125843
  34. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.
    FEBS Lett. 1997 Jan 2;400(1):25-30 PMID: 9000507
  35. Attenuated T2 relaxation by mutual cancellation of dipole-dipole coupling and chemical shift anisotropy indicates an avenue to NMR structures of very large biological macromolecules in solution.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12366-71 PMID: 9356455
  36. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins.
    FASEB J. 1997 Jan;11(1):68-76 PMID: 9034168
  37. A robust and cost-effective method for the production of Val, Leu, Ile (delta 1) methyl-protonated 15N-, 13C-, 2H-labeled proteins.
    J Biomol NMR. 1999 Apr;13(4):369-74 PMID: 10383198
  38. An (H)C(CO)NH-TOCSY pulse scheme for sequential assignment of protonated methyl groups in otherwise deuterated (15)N, (13)C-labeled proteins.
    J Biomol NMR. 1996 Oct;8(3):351-6 PMID: 20686885
  39. Pinning down cell signaling, cancer and Alzheimer's disease.
    Trends Biochem Sci. 2004 Apr;29(4):200-9 PMID: 15082314
  40. BRCA1 protein products ... Functional motifs...
    Nat Genet. 1996 Jul;13(3):266-8 PMID: 8673121
  41. The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations.
    Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2357-62 PMID: 14983014
  42. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.
    Nat Struct Biol. 2001 Oct;8(10):838-42 PMID: 11573086
  43. Side chain NMR assignments in the membrane protein OmpX reconstituted in DHPC micelles.
    J Biomol NMR. 2002 Aug;23(4):289-301 PMID: 12398349
  44. The BRCT domain is a phospho-protein binding domain.
    Science. 2003 Oct 24;302(5645):639-42 PMID: 14576433
  45. Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation.
    Mol Cell Biol. 2001 May;21(10):3445-50 PMID: 11313470
  46. The use of 2H, 13C, 15N multidimensional NMR to study the structure and dynamics of proteins.
    Annu Rev Biophys Biomol Struct. 1998;27:357-406 PMID: 9646872
  47. Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1.
    Nat Struct Mol Biol. 2004 Jun;11(6):519-25 PMID: 15133503
  48. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure.
    Genes Dev. 2002 Mar 1;16(5):583-93 PMID: 11877378
Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
0969-2126
DOI
10.1016/j.str.2004.06.002
Published
2004-07-00
Pages
1137-46
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC3652423
Subset
IM
Grants
NCI NIH HHS · R01 CA089239 · United States
NCI NIH HHS · R01 CA109449 · United States
NCI NIH HHS · R01 CA 109449 · United States
NCI NIH HHS · R01 CA 89239 · United States
External Links
PubMed source DOI: 10.1016/j.str.2004.06.002 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2