SOLUTION STRUCTURE OF THE RAIDD CARD AND MODEL FOR CARD CARD INTERACTION IN CASPASE-2 AND CASPASE-9 RECRUITMENT/

Apoptosis requires recruitment of caspases by receptor-associated adap tors through hemophilic interactions between the CARDs (caspase recrui tment domains) of adaptor proteins and prodomains of caspases. We have solved the CARD structure of the RAIDD adaptor protein that recruits ICH-1/caspase-2. It consists of six tightly packed helices arranged in a topology homologous to the Fas death domain. The surface contains a basic and an acidic patch on opposite sides. This polarity is conserv ed in the ICH-1 CARD as indicated by homology modeling. Mutagenesis da ta suggest that these patches mediate CARD/CARD interaction between RA IDD and ICH-1. Subsequent modeling of the CARDs of Apaf-1 and caspase- 9, as well as Ced-4 and Ced-3, showed that the basic/acidic surface po larity is highly conserved, suggesting a general mode for CARD/CARD in teraction.