Pyrin domain

[5] Proteins containing a pyrin domain are frequently involved in programmed cell death processes including pyroptosis and apoptosis.

The core is made of highly conserved hydrophobic residues surrounded by five or six alpha helices with α1→2 linkages.

Caspase activity controls multiple downstream pathways to trigger pyroptosis and secretion of pro-inflammatory cytokines.

[7][9] The CARD recruits pro-caspase-1 which undergoes proximity induced autocleavage to form the active caspase-1 which in turn triggers maturation of IL-1β and IL-18.

Some NLRs such as NLRP1 and NLRP2 have a straightforward mechanism by which the receptor binds to a PAMP triggering its activation, oligomerization and PYD-PYD ASC recruitment.

[11] Unlike NLRPs which function in cytosolic PAMP and DAMP recognition, ALRs mainly act within the nucleus oligomerizing along the DNA staircase.

[7] Since most inflammasomes are formed by aggregation due to PYD-PYD interactions, POPs instead bind to PYDs preventing polymerization and therefore regulating and/or resolving inflammation response.

NMR structure of the NLRP7 pyrin domain [ 1 ] rendered in UCSF Chimera. [ 2 ] Mesh electrostatic potential map using Coulombic coloring is superimposed showing areas of positive residue charge in blue and negative in maroon. Circled is the distinct elongated α2-α3 loop that is characteristic of pyrin domains.
(Left) Side view of the Cryo-EM structure of AIM2 PYD filaments [ 3 ] showing homotypic PYD-PYD aggregation in inflammasome assembly. (Right) Top down view of same filaments with hydrophobic residues in cyan forming symmetry around the center. Both rendered in UCSF chimera. [ 2 ]