Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4

Cell. 2010 Apr 30;141(3):446-57. doi: 10.1016/j.cell.2010.03.017.


The CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death in Caenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How the CED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystal structure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organized as a tetramer of an asymmetric dimer via a previously unreported interface among AAA(+) ATPases. These eight CED-4 molecules form a funnel-shaped structure. The mature CED-3 protease is monomeric in solution and forms an active holoenzyme with the CED-4 apoptosome, within which the protease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosome appears to bind only two, not eight, molecules of mature CED-3. The structure of the CED-4 apoptosome reveals shared principles for the NB-ARC family of AAA(+) ATPases and suggests a mechanism for the activation of CED-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosomes / metabolism
  • Apoptotic Protease-Activating Factor 1 / metabolism
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry*
  • Calcium-Binding Proteins / chemistry*
  • Caspases / chemistry
  • Crystallography, X-Ray
  • Models, Molecular
  • Sequence Alignment
  • X-Ray Diffraction


  • Apoptosomes
  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • Ced-4 protein, C elegans
  • Caspases
  • ced-3 protein, C elegans

Associated data

  • PDB/3LQQ
  • PDB/3LQR