CARD Domain |
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Class:Apoptosis |
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Structure:
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. |
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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.
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Examples of Proteins:
CARD protein |
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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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Referenced in part on Cell Signaling Technology Website, Reference Section on Protein Domains. We gratefully acknowledge the following contributors:
Piers Nash1, Dan Lin3, Kathleen Binns2, Clark Wells2, Rob Ingham2, Terry Kubiseski2, Bernard Liu1, Matt Smith2,3, Ivan Blasutig2,3, Maria Sierra1, Caesar Lim2,3, Michael Arc1, Jim Fawcett2 and Tony Pawson2,3.
1. Ben May Institute for Cancer Research, The University of Chicago, Chicago, Illinois, 60637, USA
2. Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada
3. Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
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