The death domain superfamily: a tale of two interfaces?

The death domain superfamily, composed of the death domain (DD), death effe ctor domain (DED) and caspase recruitment domain (CARD) families of protein s, plays a pivotal role in signaling events that regulate apoptosis. This r eview compares and contrasts the ten superfamily members with known structu res. In particular the two heterodimerization modes described to date, the CARD-CARD interaction between human Apaf-1 and procaspase 9, and the DD-DD interaction between Drosophila Pelle and Tube, are examined. The dimerizati on modes are strikingly different and, importantly, are not mutually exclus ive. In fact, a trimer can be formed using both interactions.