Assembly of Bak homodimers into higher order homooligomers in the mitochondrial apoptotic pore

Sci Rep. 2016 Aug 4;6:30763. doi: 10.1038/srep30763.


In mitochondrial apoptosis, Bak is activated by death signals to form pores of unknown structure on the mitochondrial outer membrane via homooligomerization. Cytochrome c and other apoptotic factors are released from the intermembrane space through these pores, initiating downstream apoptosis events. Using chemical crosslinking and double electron electron resonance (DEER)-derived distance measurements between specific structural elements in Bak, here we clarify how the Bak pore is assembled. We propose that previously described BH3-in-groove homodimers (BGH) are juxtaposed via the 'α3/α5' interface, in which the C-termini of helices α3 and α5 are in close proximity between two neighboring Bak homodimers. This interface is observed concomitantly with the well-known 'α6:α6' interface. We also mapped the contacts between Bak homodimers and the lipid bilayer based on EPR spectroscopy topology studies. Our results suggest a model for the lipidic Bak pore, whereby the mitochondrial targeting C-terminal helix does not change topology to accommodate the lining of the pore lumen by BGH.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Binding Sites
  • Cells, Cultured
  • Crystallography, X-Ray
  • Electron Spin Resonance Spectroscopy
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Lipid Bilayers / metabolism
  • Mice
  • Mitochondria / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • bcl-2 Homologous Antagonist-Killer Protein / chemistry*
  • bcl-2 Homologous Antagonist-Killer Protein / metabolism*


  • Bak1 protein, mouse
  • Lipid Bilayers
  • bcl-2 Homologous Antagonist-Killer Protein