Pyrin domain

Death domain (DD) superfamily consists of structurally related homotypic interaction motifs of approximately 90 amino acids. The motifs are organized in six antiparallel amphipathic a-helices, the so-called DD fold. The four members of the super family are the death domain (DD), the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the Pyrin domain. All are important mediators for the assembly of caspase activating complexes. 

Structural studies have revealed that several other domains involved in cell death and inflammatory signaling transduction, including the death effector domain (DED) (Fig. 11C), the caspase recruitment domain (CARD) and the Pyrin domain (PYD), also possess the same six helix bundle structures of DDs (Chou et al, 1998 Eberstadt et al, 1998 Hiller et al, 2003), forming the death domain superfamily. Interestingly, interactions have only been observed among proteins within the same subfamilies with no cross interactions between proteins from different subfamilies. 

Hiller, S., Kohl, A., Fiorito, F., Herrmann, T., Wider, G., Tschopp, J., Grutter, M. G., and Wuthrich, K. (2003). NMR structure of the apoptosis- and inflammation-related NALPl pyrin domain. Structure (Camb) 11, 1199-1205. 

Recruitment of the initiator procaspases into a multiprotein complex results from a regulated series of protein-protein interactions mediated by interaction modules . Four types of interaction modules are involved in the activation of initiator caspases and thus play important roles in the initiation of apoptosis (review Weber and Vin-cenz, 2001). These domains have been named the death domain (DD),, the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the less characterized pyrin domain. The domains are found on several components of the apoptotic signaling pathways and mediate homotypic protein-protein interactions, i. e., a given module will interact only with a member of the same family and not with members of the other families. Since members of the same module are found on different proteins, these modules mediate the assembly of hetero-oligomeric protein complexes. As examples, DDs are found on death receptors and their cofactors, D EDs on cofactors and the initiator caspase-8, and CARDS on cofactors, caspase-2, and caspase-9. 

Werts, C, S. E. Girardin, et al. (2006). "IIK, CARD and PYRIN three domains for an antimicrobial triad." Cell DeaBt Differ. 13 798-815. 

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