The CED-4 homo-oligomer or apoptosome is required for initiation of programmed cell death inCaenorhabditis elegans by facilitating autocatalytic activation of the CED-3 caspase zymogen. How theCED-4 apoptosome assembles and activates CED-3 remains enigmatic. Here we report the crystalstructure of the complete CED-4 apoptosome and show that it consists of eight CED-4 molecules, organizedas 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 theprotease activity of CED-3 is markedly stimulated. Unexpectedly, the octameric CED-4 apoptosomeappears 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.

Dang SY, Sun LF, Huang YG, Lu FR, Liu YF, Gong HP, Wang JW, Yan N. Structure of a fucose transporter in an outward-open conformation. Nature. 2010, 467:734-739.