2K7W

BAX Activation is Initiated at a Novel Interaction Site


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 1500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

BAX activation is initiated at a novel interaction site.

Gavathiotis, E.Suzuki, M.Davis, M.L.Pitter, K.Bird, G.H.Katz, S.G.Tu, H.C.Kim, H.Cheng, E.H.Tjandra, N.Walensky, L.D.

(2008) Nature 455: 1076-1081

  • DOI: https://doi.org/10.1038/nature07396
  • Primary Citation of Related Structures:  
    2K7W

  • PubMed Abstract: 

    BAX is a pro-apoptotic protein of the BCL-2 family that is stationed in the cytosol until activated by a diversity of stress stimuli to induce cell death. Anti-apoptotic proteins such as BCL-2 counteract BAX-mediated cell death. Although an interaction site that confers survival functionality has been defined for anti-apoptotic proteins, an activation site has not been identified for BAX, rendering its explicit trigger mechanism unknown. We previously developed stabilized alpha-helix of BCL-2 domains (SAHBs) that directly initiate BAX-mediated mitochondrial apoptosis. Here we demonstrate by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins. The specificity of the human BIM-SAHB-BAX interaction is highlighted by point mutagenesis that disrupts functional activity, confirming that BAX activation is initiated at this novel structural location. Thus, we have now defined a BAX interaction site for direct activation, establishing a new target for therapeutic modulation of apoptosis.


  • Organizational Affiliation

    Department of Pediatric Oncology and the Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts 02115, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Apoptosis regulator BAX192Homo sapiensMutation(s): 0 
Gene Names: BAX
UniProt & NIH Common Fund Data Resources
Find proteins for Q07812 (Homo sapiens)
Explore Q07812 
Go to UniProtKB:  Q07812
PHAROS:  Q07812
GTEx:  ENSG00000087088 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07812
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-like protein 1120Homo sapiensMutation(s): 0 
Gene Names: BCL2L11
UniProt & NIH Common Fund Data Resources
Find proteins for O43521 (Homo sapiens)
Explore O43521 
Go to UniProtKB:  O43521
PHAROS:  O43521
GTEx:  ENSG00000153094 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO43521
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 1500 
  • 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: 2008-10-21
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Database references, Derived calculations