2M04

Solution structure of BCL-xL in complex with PUMA BH3 peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • 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

PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis.

Follis, A.V.Chipuk, J.E.Fisher, J.C.Yun, M.K.Grace, C.R.Nourse, A.Baran, K.Ou, L.Min, L.White, S.W.Green, D.R.Kriwacki, R.W.

(2013) Nat Chem Biol 9: 163-168

  • DOI: https://doi.org/10.1038/nchembio.1166
  • Primary Citation of Related Structures:  
    2M03, 2M04, 4HNJ

  • PubMed Abstract: 

    Following DNA damage, nuclear p53 induces the expression of PUMA, a BH3-only protein that binds and inhibits the antiapoptotic BCL-2 repertoire, including BCL-xL. PUMA, unique among BH3-only proteins, disrupts the interaction between cytosolic p53 and BCL-xL, allowing p53 to promote apoptosis via direct activation of the BCL-2 effector molecules BAX and BAK. Structural investigations using NMR spectroscopy and X-ray crystallography revealed that PUMA binding induced partial unfolding of two α-helices within BCL-xL. Wild-type PUMA or a PUMA mutant incapable of causing binding-induced unfolding of BCL-xL equivalently inhibited the antiapoptotic BCL-2 repertoire to sensitize for death receptor-activated apoptosis, but only wild-type PUMA promoted p53-dependent, DNA damage-induced apoptosis. Our data suggest that PUMA-induced partial unfolding of BCL-xL disrupts interactions between cytosolic p53 and BCL-xL, releasing the bound p53 to initiate apoptosis. We propose that regulated unfolding of BCL-xL provides a mechanism to promote PUMA-dependent signaling within the apoptotic pathways.


  • Organizational Affiliation

    Department of Structural Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-like protein 1180Homo sapiensMutation(s): 0 
Gene Names: BCL2-like 1BCL2LBCL2L1BCLX
UniProt & NIH Common Fund Data Resources
Find proteins for Q07817 (Homo sapiens)
Explore Q07817 
Go to UniProtKB:  Q07817
PHAROS:  Q07817
GTEx:  ENSG00000171552 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07817
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Bcl-2-binding component 325Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q9BXH1 (Homo sapiens)
Explore Q9BXH1 
Go to UniProtKB:  Q9BXH1
PHAROS:  Q9BXH1
GTEx:  ENSG00000105327 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9BXH1
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • 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: 2013-01-30
    Type: Initial release
  • Version 1.1: 2013-02-06
    Changes: Database references
  • Version 1.2: 2013-03-06
    Changes: Database references
  • Version 1.3: 2024-05-01
    Changes: Data collection, Database references