5FMK

Bcl-xL with Bak BH3 complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Physiological Restraint of Bak by Bcl-Xl is Essential for Cell Survival.

Lee, E.F.Grabow, S.Chappaz, S.Dewson, G.Hockings, C.Kluck, R.M.Gray, D.H.Witkowski, M.T.Evangelista, M.Pettikiriarachchi, A.Bouillet, P.Lane, R.M.Czabotar, P.E.Colman, P.M.Smith, B.J.Kile, B.T.Fairlie, W.D.

(2016) Genes Dev 30: 1240

  • DOI: https://doi.org/10.1101/gad.279414.116
  • Primary Citation of Related Structures:  
    5FMI, 5FMJ, 5FMK

  • PubMed Abstract: 

    Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. Mechanistic insights have primarily been gleaned from in vitro studies because genetic approaches in mammals that produce unambiguous data are difficult to design. Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. In vitro, Bak(Q75L) cells were significantly more sensitive to various apoptotic stimuli. In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak.


  • Organizational Affiliation

    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia; Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria 3086, Australia; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia; School of Cancer Medicine, La Trobe University, Melbourne, Victoria 3084, Australia.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BCL-XL158Homo sapiensMutation(s): 0 
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:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
BCL-2 HOMOLOGOUS ANTAGONIST/KILLER34Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q16611 (Homo sapiens)
Explore Q16611 
Go to UniProtKB:  Q16611
PHAROS:  Q16611
GTEx:  ENSG00000030110 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16611
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.73 Å
  • R-Value Free: 0.186 
  • R-Value Work: 0.158 
  • R-Value Observed: 0.159 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.668α = 90
b = 55.459β = 127.12
c = 61.053γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-06-01
    Type: Initial release
  • Version 1.1: 2016-06-08
    Changes: Database references
  • Version 1.2: 2017-11-08
    Changes: Source and taxonomy
  • Version 1.3: 2024-01-10
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description