4IFI

Structure of human BRCA1 BRCT in complex with BAAT peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Basis for the BRCA1 BRCT Interaction with the Proteins ATRIP and BAAT1.

Liu, X.Ladias, J.A.

(2013) Biochemistry 52: 7618-7627

  • DOI: https://doi.org/10.1021/bi400714v
  • Primary Citation of Related Structures:  
    4IFI, 4IGK

  • PubMed Abstract: 

    The breast and ovarian cancer susceptibility protein 1 (BRCA1) plays a central role in DNA damage response (DDR). Two tandem BRCA1 C-terminal (BRCT) domains interact with several proteins that function in DDR and contain the generally accepted motif pS-X-X-F (pS denoting phosphoserine and X any amino acid), including the ATR-interacting protein (ATRIP) and the BRCA1-associated protein required for ATM activation-1 (BAAT1). The crystal structures of the BRCA1 BRCTs bound to the phosphopeptides ATRIP (235-PEACpSPQFG-243) and BAAT1 (266-VARpSPVFSS-274) were determined at 1.75 Å and 2.2 Å resolution, respectively. The pSer and Phe(+3) anchor the phosphopeptides into the BRCT binding groove, with adjacent peptide residues contributing to the interaction. In the BRCA1-ATRIP structure, Gln(+2) is accommodated through a conformational change of the BRCA1 E1698 side chain. Importantly, isothermal titration calorimetry experiments showed that the size and charge of the side chains at peptide positions +1 and +2 contribute significantly to the BRCA1 BRCT-peptide binding affinity. In particular, the Asp(+1) and Glu(+2) in the human CDC27 peptide 816-HAAEpSDEF-823 abrogate the interaction with the BRCA1 BRCTs due in large part to electrostatic repulsion between Glu(+2) and E1698, indicating a preference of these domains for specific side chains at positions +1 and +2. These results emphasize the need for a systematic assessment of the contribution of the peptide residues surrounding pSer and Phe(+3) to the binding affinity and specificity of the BRCA1 BRCTs in order to elucidate the molecular mechanisms underlying the hierarchy of target selection by these versatile domains during DDR and tumorigenesis.


  • Organizational Affiliation

    Molecular Medicine Laboratory and Macromolecular Crystallography Unit, Department of Medicine, Harvard Medical School , Boston Massachusetts 02215, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Breast cancer type 1 susceptibility protein214Homo sapiensMutation(s): 0 
Gene Names: BRCA1RNF53
EC: 6.3.2
UniProt & NIH Common Fund Data Resources
Find proteins for P38398 (Homo sapiens)
Explore P38398 
Go to UniProtKB:  P38398
PHAROS:  P38398
GTEx:  ENSG00000012048 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP38398
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
BAAT peptide6Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q6PJG6 (Homo sapiens)
Explore Q6PJG6 
Go to UniProtKB:  Q6PJG6
PHAROS:  Q6PJG6
GTEx:  ENSG00000106009 
Entity Groups  
UniProt GroupQ6PJG6
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ACT
Query on ACT

Download Ideal Coordinates CCD File 
C [auth A]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
B
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.20 Å
  • R-Value Free: 0.261 
  • R-Value Work: 0.197 
  • R-Value Observed: 0.200 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 65.22α = 90
b = 65.22β = 90
c = 91.356γ = 120
Software Package:
Software NamePurpose
CBASSdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-10-30
    Type: Initial release
  • Version 1.1: 2013-12-25
    Changes: Database references
  • Version 1.2: 2023-09-20
    Changes: Data collection, Database references, Derived calculations, Refinement description