1OQA

Solution structure of the BRCT-c domain from human BRCA1


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 250 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Solution structure, backbone dynamics, and association behavior of the C-terminal BRCT domain from the breast cancer-associated protein BRCA1.

Gaiser, O.J.Ball, L.J.Schmieder, P.Leitner, D.Strauss, H.Wahl, M.Kuhne, R.Oschkinat, H.Heinemann, U.

(2004) Biochemistry 43: 15983-15995

  • DOI: https://doi.org/10.1021/bi049550q
  • Primary Citation of Related Structures:  
    1OQA

  • PubMed Abstract: 

    BRCA1 is a tumor suppressor protein associated with breast and ovarian cancer. The C-terminal region of BRCA1 consists of two closely spaced BRCT domains which mediate essential biological functions, including regulation of transcription and control of cell-cycle progression by their interaction with phosphorylated effector proteins. Here we report the NMR structure of the isolated C-terminal BRCT domain (BRCT-c) from human BRCA1. BRCT-c is well-structured in solution, folding independently in the absence of its BRCT-n counterpart. Ultracentrifugation experiments and size exclusion chromatography reveal that BRCT-c exists as a monomer under near-physiological conditions. Dynamics measurements from NMR data show three loops which coincide with the most variable sequence regions in BRCT domains, to be genuinely flexible in solution. The solution structure of BRCT-c shows subtle conformational changes when compared to the crystal structure of BRCT-c in the tandem repeat of BRCA1. These affect sites involved in formation of the BRCT-n-BRCT-c interface and the binding to phosphoserine-containing peptides. The results suggest that the presence of native BRCT-n and a properly aligned BRCT-n-BRCT-c interface are essential if BRCT-c is to adopt a biologically active conformation. Structural consequences of cancer-associated mutations and biological implications of the dynamic behavior are discussed.


  • Organizational Affiliation

    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Breast cancer type 1 susceptibility protein110Homo sapiensMutation(s): 0 
Gene Names: BRCA1
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
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 250 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-06-15
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-23
    Changes: Data collection, Database references, Derived calculations