CARD Domain

No Image CARDs are members of the death-fold superfamily, sharing the six helix bundle with greek key topology with the Death domain and Death effector domain (DED). Helices are stacked in pairs and packed in an antiparallel manner, enclosing the tightly packed hydrophobic core. As in other superfamily members, the charged residues of CARDs are polarized with basic residues primarily found on one side of the module (a 1,3,4) and acidic residues on the opposite surface (a 2,5,6). Although topology is identical and a 2-5 are superimposable between CARDs and Death domains, the orientation and length of a1 and a6 vary between the two modules (see Death domains). The structure shown is the card domain Apaf-1.

Structure Reference:
Day, CL. et al. (1999) Cell Death Differ. 6(11):1125-32. PDB: 1CWW.

Domain binding and function:
Caspase recruitment domains (CARDs) are modules of 90 - 100 amino acids involved in apoptosis signaling pathways. CARDs mediate the association of adaptor proteins and procaspases through heterodimerization of the respective CARDs, recruiting procaspases to upstream signaling complexes and allowing autoactivation. Dimerization of CARDs is believed to be mediated primarily by electrostatic interactions between complementary charged surfaces with a binding specificity achieved by particular charge patterns between CARD binding partners.
Examples of Proteins: 
CARD protein
Caspase CARD binding partner
RAIID Adaptor protein Pro-Caspase 2
APAF-1 Binds Cytochrome C and dATP Pro-Caspase 9
CARDIAK Ser/Thr Kinase Pro-Caspase 1

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