conformational change, maybe by extracting the CARD domain out of an inhibitory
interaction adopted in the nonsignaling state. It is tempting to speculate that other
proteins of this architecture act in a similar manner: the C-terminal LRR domains
could be sensors for as yet unknown factors that trigger the recruitment of CARD-,
PYD-, or TIR-containing proteins into a complex similar to the apoptosome. Future
experiments are going to show whether there is some truth to these predictions made
from the domain content.
The domain descriptions and architectural considerations presented in the previous
sections can give only a very cursory overview of the present knowledge. For more
focused analysis, the reader is referred to some topical reviews on domain structure
(Liang and Fesik, 1997; Fesik, 2000), domain evolution (Aravind et al., 1999; 2001),
and domain interaction patterns (Darnay and Aggarwal, 1997; Hofmann, 1999;
Weber and Vincenz, 200 1a). We cannot help but be fascinated by the intricate ways
that nature reuses, shuffles, and reassembles a limited domain repertoire, resulting in
a finely tuned signaling network that controls the most important aspect of cell
biology: life or death.
96 GENETICS OF APOPTOSIS