BCL-XL dimerization by three-dimensional domain swapping

J Mol Biol. 2006 Feb 17;356(2):367-81. doi: 10.1016/j.jmb.2005.11.032. Epub 2005 Dec 1.


Dimeric interactions among anti- and pro-apoptotic members of the BCL-2 protein family are dynamically regulated and intimately involved in survival and death functions. We report the structure of a BCL-X(L) homodimers a 3D-domain swapped dimer (3DDS). The X-ray crystal structure demonstrates the mutual exchange of carboxy-terminal regions including BH2 (Bcl-2 homology 2) between monomer subunits, with the hinge region occurring at the hairpin turn between the fifth and sixth alpha helices. Both BH3 peptide-binding hydrophobic grooves are unoccupied in the 3DDS dimer and available for BH3 peptide binding, as confirmed by sedimentation velocity analysis. BCL-X(L) 3DDS dimers have increased pore-forming activity compared to monomers, suggesting that 3DDS dimers may act as intermediates in membrane pore formation. Chemical crosslinking studies of Cys-substituted BCL-X(L) proteins demonstrate that 3DDS dimers form in synthetic lipid vesicles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cross-Linking Reagents / chemistry
  • Crystallography, X-Ray
  • Dimerization
  • Humans
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Structure, Quaternary*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / metabolism
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • bcl-X Protein / chemistry*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism


  • BCL2L1 protein, human
  • Bax protein (53-86)
  • Cross-Linking Reagents
  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • bcl-X Protein