Apaf-1

The N-terminal 85 amino acids of this 130 kDa protein are homologous to the CARD segment in the pro-domain of several caspases, e.g. CED-3, Caspase-1, caspase-2, and Caspase-9. CARDs have been proposed to mediate the recruitment of caspases (Hofmann et al., 1997, Trends Biochem. Sci., 257: 155-156). Indeed, the CARD of Apaf-1 was shown to bind to Caspase-9, but only in the presence of dATP and Cytochrome c. Furthermore, Apaf-1 was reported to associate with other caspases which contain CARDs within their long prodomain, i.e. Caspase-4 and Caspase-8 (Hu et al., 1998, Proc. Nat. Acad. Sci. USA, 95: 4386-4391)! The N-terminal CARD domain is followed by a stretch of 320 aa that is homolog to CED-4; the highest homology is found within the so called Walker's A- and B-box consensus sequences for nucleotide binding sites. Several aa residues that are required for CED-4 activity are conserved in Apaf-1 (Yuan and Horvitz, 1990, Dev. Biol., 138: 33-41). The C-terminal segment of Apaf-1 contains 12 WD-40 repeats.