CARD (domain)

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PDB 3crd EBI

CARD (Caspase Recruitment Domain) is a protein interaction domain that is found in a variety of proteins involved in apoptosis (programmed cell death), inflammation, and immune system signaling. This domain enables proteins to form complexes with other CARD-containing proteins, facilitating the transmission of signals within cells that can lead to inflammatory responses or cell death.

Structure and Function

The CARD domain is typically composed of six or seven alpha-helices. It mediates homotypic protein-protein interactions, meaning it binds to other CARD domains in a specific manner. This interaction is crucial for the assembly of large signaling complexes known as inflammasomes, which are essential for the activation of inflammatory responses and apoptosis.

CARD domains are found in various proteins, including members of the caspase family, which are central to the execution of apoptosis, and proteins involved in the regulation of NF-κB signaling pathways, which play a key role in immune and inflammatory responses. For example, the protein Caspase-9 contains a CARD domain that is essential for its activation and the initiation of the apoptotic cascade.

Role in Disease

Mutations or dysregulation of CARD-containing proteins can lead to a variety of diseases. For instance, inappropriate activation of inflammasomes can result in autoinflammatory diseases, while defects in apoptotic signaling pathways can contribute to cancer development and progression. Understanding the mechanisms by which CARD domains mediate protein interactions and signal transduction is therefore of significant interest for the development of therapeutic strategies targeting these pathways.

Examples of CARD-Containing Proteins

- Caspase-1: Involved in the processing and activation of pro-inflammatory cytokines. - Caspase-9: Plays a critical role in the initiation of apoptosis. - NOD-like receptors (NLRs): A family of intracellular receptors that detect microbial motifs and danger signals, leading to the activation of inflammatory responses. - Apoptosis-associated speck-like protein containing a CARD (ASC): Acts as an adaptor protein in the formation of inflammasomes.

Research and Therapeutic Implications

Research into CARD domains and their containing proteins is ongoing, with the aim of understanding their precise roles in health and disease. By targeting specific interactions between CARD domains, it may be possible to develop drugs that can modulate inflammatory responses or induce apoptosis in cancer cells. Such therapeutic strategies could offer new treatments for inflammatory diseases, autoimmune disorders, and cancer.