2K86

Solution Structure of FOXO3a Forkhead domain


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • 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

Biochemical and structural characterization of an intramolecular interaction in FOXO3a and its binding with p53.

Wang, F.Marshall, C.B.Yamamoto, K.Li, G.Y.Plevin, M.J.You, H.Mak, T.W.Ikura, M.

(2008) J Mol Biol 384: 590-603

  • DOI: https://doi.org/10.1016/j.jmb.2008.09.025
  • Primary Citation of Related Structures:  
    2K86

  • PubMed Abstract: 

    FOXO3a, a forkhead transcription factor and member of the forkhead box class O (FOXO) subfamily, has been shown to promote the translocation of p53 to the cytoplasm, thereby inducing the mitochondria-associated apoptotic pathway. However, the binding sites that mediate this interaction between FOXO3a and p53 have not been identified. Here, we show that two regions within FOXO3a, the forkhead (FH) DNA binding domain and a conserved C-terminal transactivation domain (CR3), interact with the DNA binding domain of p53, with affinities in the low millimolar range and low micromolar range, respectively. Our data further suggest that within the FOXO3a molecule, the FH and CR3 domains engage in an intramolecular interaction with low micromolar affinity. Moreover, we used NMR to determine the solution structure of the FH domain. This enabled us to map the binding site for the CR3, which overlaps with the DNA binding site. We demonstrate that an intrinsically disordered linker between the FH and CR3 domains is required for full p53 binding activity. We also show that p53 disrupts the intramolecular interaction between FH and CR3. These results provide evidence for interplay of the FH and CR3 domains in association with p53.


  • Organizational Affiliation

    Division of Signaling Biology, Ontario Cancer Institute, Toronto, Ontario, Canada M5G 2M9.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Forkhead box protein O3103Homo sapiensMutation(s): 0 
Gene Names: FOXO3FKHRL1FOXO3A
UniProt & NIH Common Fund Data Resources
Find proteins for O43524 (Homo sapiens)
Explore O43524 
Go to UniProtKB:  O43524
PHAROS:  O43524
GTEx:  ENSG00000118689 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43524
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 20 
  • 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: 2008-10-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-02-19
    Changes: Data collection, Database references, Derived calculations, Other
  • Version 1.3: 2024-05-01
    Changes: Data collection, Database references