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 adaptors through homophilic interactions between the CARDs (caspase recruitment 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 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.
Committee on Higher Degrees in Biophysics, Harvard University, Cambridge, Massachusetts 02138, USA.
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Chou
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Matsuo
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Duan
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Wagner
D000595:Amino Acid Sequence; D053477:Apoptotic Protease-Activating Factor 1; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics; D053143:Caspase 2; D053453:Caspase 9; D020169:Caspases; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D016415:Sequence Alignment
D053477:Apoptotic Protease-Activating Factor 1; D002352:Carrier Proteins; D011506:Proteins; D053143:Caspase 2; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases