Apoptosome

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The apoptosome is a large ternary protein structure formed in the process of apoptosis. Its formation is triggered by the release of cytochrome c from the mitochondria in response to an internal (intrinsic) or external (extrinsic) cell death stimulus. Stimuli can vary from DNA damage and viral infection to developmental cues such as the loss of tadpole's tail.

Once cytochrome c is released, it binds to the cytosolic protein Apaf-1 in what is believed to be a two to one ratio of cytochrome c to apaf-1. It has also been shown that the nucleotide dATP as third component binds to apaf-1 however its exact role is still debated. The formation, the apoptosome, had never been crystallized but APAF-1/cytochrome-c apoptosome has been imaged at lower (2 nm) resolution by cryogenic scanning electron microscopy, revealing a wheel-like particle with 7-fold symmetry. Using molecular modeling it was possible to infer likely positions of all the APAF-1 domains (CARD, NBARC and WD40) and cytochrome c. Once formed, the apoptosome can then recruit and activate the inactive pro-caspase-9. Once activated, this caspase can then activate other caspases and trigger a cascade of events leading to apoptosis.

Neither the apoptosome nor mitochondria are involved in the extrinsic death receptor pathway.

References

Acehan D, Jiang X, Morgan DG, Heuser JE, Wang X, Akey CW "Three-dimensional structure of the apoptosome: implications for assembly, procaspase-9 binding, and activation." Mol Cell. 2002 Feb;9(2):423-32.



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