Apoptosomes and programmed cell death
Programmed cell death pathways have evolved in eukaryotes to provide appropriate responses to developmental cues and cell stress. Thus, the intrinsic death pathway plays an important role in sculpting tissues by removing unwanted cells and also provides a line of defense against pathogens and unrestricted cell growth. The importance of this death pathway is underscored by its conservation in animal cells.
In the intrinsic pathway, apoptotic stimuli trigger the release of cytochrome c from mitochondria. Apaf-1 then binds to cytochrome c and assembles into a large, procaspase activation platform. Apaf-1 and its Drosophila homolog (Dark) are cardinal members of the NOD branch of the P-loop, NTPase super-family. We are studying the structures of the Apaf-1 and Dark apoptosome, both in the ground state and after binding their apical procaspase. This will provide information on how they function as cell killing machines.