3PK1

Crystal structure of Mcl-1 in complex with the BaxBH3 domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Mutation to Bax beyond the BH3 domain disrupts interactions with pro-survival proteins and promotes apoptosis

Czabotar, P.E.Lee, E.F.Thompson, G.V.Wardak, A.Z.Fairlie, W.D.Colman, P.M.

(2011) J Biol Chem 286: 7123-7131

  • DOI: https://doi.org/10.1074/jbc.M110.161281
  • Primary Citation of Related Structures:  
    3PK1, 3PL7

  • PubMed Abstract: 

    Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic activity of Bax, either directly through interactions with Bax or indirectly by sequestration of activator BH3-only proteins, or both. Mutations in Bax that promote apoptosis can provide insight into how Bax is regulated. Here, we describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-x(L) in complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These structures reveal canonical interactions between four signature hydrophobic amino acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival proteins. In both structures, Met-74 from the Bax peptide engages with the BH3-binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants disrupt interactions between Bax and all pro-survival proteins, but these Bax mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in colony assays even in the absence of an external apoptotic stimulus. These results support a model in which direct restraint of Bax by pro-survival Bcl-2 proteins is a barrier to apoptosis.


  • Organizational Affiliation

    Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia. czabotar@wehi.edu.au


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Induced myeloid leukemia cell differentiation protein Mcl-1
A, C
189Homo sapiensMutation(s): 0 
Gene Names: MCL1BCL2L3
UniProt & NIH Common Fund Data Resources
Find proteins for Q07820 (Homo sapiens)
Explore Q07820 
Go to UniProtKB:  Q07820
PHAROS:  Q07820
GTEx:  ENSG00000143384 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ07820
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Apoptosis regulator BAX
B, D
34Homo sapiensMutation(s): 0 
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
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CD
Query on CD

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A],
L [auth A],
M [auth B],
N [auth B],
O [auth C],
P [auth C],
Q [auth C],
R [auth C],
S [auth C],
T [auth C],
U [auth D],
V [auth D]
CADMIUM ION
Cd
WLZRMCYVCSSEQC-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.212 
  • R-Value Observed: 0.213 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 97.923α = 90
b = 81.469β = 124.23
c = 57.927γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-12-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-01-22
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description