title: Apoptosome structure, assembly, and procaspase activation.
abstract: Apaf-1-like molecules assemble into a ring-like platform known as the apoptosome. This cell death platform then activates procaspases in the intrinsic cell death pathway. In this review, crystal structures of Apaf-1 monomers and CED-4 dimers have been combined with apoptosome structures to provide insights into the assembly of cell death platforms in humans, nematodes, and flies. In humans, the caspase recognition domains (CARDs) of procaspase-9 and Apaf-1 interact with each other to form a CARD-CARD disk, which interacts with the platform to create an asymmetric proteolysis machine. The disk tethers multiple pc-9 catalytic domains to the platform to raise their local concentration, and this leads to zymogen activation. These findings have now set the stage for further studies of this critical activation process on the apoptosome.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany Street, Boston, MA 02118, USA.
authors.forename: Shujun
authors.initials: S
authors.lastname: Yuan
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Akey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000378:metabolism; D053478:Apoptosomes / Q000737:chemistry* / Q000378:metabolism; D053477:Apoptotic Protease-Activating Factor 1 / Q000737:chemistry* / Q000378:metabolism; D017173:Caenorhabditis elegans; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism*; D019281:Dimerization; D004330:Drosophila; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013045:Species Specificity
chemical_list: D051017:Apoptosis Regulatory Proteins; D053478:Apoptosomes; D053477:Apoptotic Protease-Activating Factor 1; C485604:CASP8AP2 protein, human; D002135:Calcium-Binding Proteins; D053453:Caspase 9
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