Solution Structure of the RAIDD CARD and Model for CARD/CARD Interaction in Caspase-2 and Caspase-9 Recruitment

• Published in: Cell Vol. 94; no. 2; pp. 171 - 180
• Main Authors: Chou, James J, Matsuo, Hiroshi, Duan, Hanjun, Wagner, Gerhard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.07.1998
• Subjects: Amino Acid Sequence; Apoptotic Protease-Activating Factor 1; Carrier Proteins - chemistry; Carrier Proteins - genetics; Caspase 2; Caspase 9; Caspases; Crystallography, X-Ray; Cysteine Endopeptidases - chemistry; Models, Molecular; Molecular Sequence Data; Mutagenesis; Nuclear Magnetic Resonance, Biomolecular; Protein Conformation; Protein Structure, Secondary; Proteins - chemistry; Sequence Alignment
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)81417-8

Apoptosis requires recruitment of caspases by receptor-associated adaptors through homophilic interactions between the CARDs ( ca spase r ecruitment d omains) 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 conserved in the ICH-1 CARD as indicated by homology modeling. Mutagenesis data suggest that these patches mediate CARD/CARD interaction between RAIDD 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 polarity is highly conserved, suggesting a general mode for CARD/CARD interaction.