FIGURE 4.

Model of the mechanism of apoptosome formation. A, autoinhibited Apaf-1. Two blocking fixtures secure the closed state as follows: interactions between the WD40 propellers and the NOD (indicated by a gray rectangle protruding from one of the gray ovals) and interactions between subdomains of the NOD (indicated by tight arrangement of the blue oval and the blue triangle). B, Apaf-1 liganded with ATP. The presence of the γ-phosphate weakens subdomain interactions within the NOD (indicated by a gap between the blue oval and the blue triangle). Cyt. c, cytochrome c. C, Apaf-1 liganded with cytochrome c. Blocking interactions between WD40 propellers and the NOD are released. D, Apaf-1 liganded with cytochrome c and ATP. Both blocking fixtures are removed. E, open Apaf-1 ready to assemble into the apoptosomal heptamer.