N by foreign organisms and recognizes pathogens within a nonspecific manner (Akira et al., 2006). Nucleic acids, the key macromolecules for life, are potent triggers on the innate immune response. Not too long ago, a variety of RNA/DNA-recognizing receptors have already been reported (Barbalat et al., 2011). Amongst the diverse DNA receptors, human AIM2 (absent in melanoma 2) and IFI16 (-interferon-inducible protein 16) are each members of the HIN-200 protein family (haematopoietic interferon-inducible nuclear proteins containing a 200-amino-acid signature repeat; Dawson Trapani, 1996). The structurally and functionally associated HIN-200 family comprises four human members and 14 verified or putative murine proteins (Ludlow et al., 2005), and most of them include two kinds of functional domains: a pyrin domain (PYD) in the N-terminus and one or two copies from the signature HIN domain at the C-terminus (Schattgen Fitzgerald, 2011; Hornung et al., 2009). The PYD domain adopts the death-domain fold, which has been identified in quite a few proteins involved in inflammation-related or apoptosis-related processes (Park, 2012). The death domains are evolutionarily conserved and comprise an antiparallel -helical bundle. The PYD domains with the HIN-200 proteins engage in homotypic protein?protein interactions to form substantial complexes (Kersse et al., 2011; Park et al., 2007), and their HIN domains can mediate DNA binding and/or protein rotein interaction (Ludlow et al., 2005; Schattgen Fitzgerald, 2011). As an example, the HIN domain of AIM2 interacts with cytoplasmic DNA and its PYD domain binds towards the adaptor protein ASC (apoptosis-associated speck-like protein containing a caspaserecruitment domain). ASC can additional recruit the effector enzyme procaspase-1, resulting inside the formation from the significant signalling complicated inflammasome and the activation of inflammatory responsesdoi:ten.1107/S2053230X1303135X# 2014 International Union of Crystallography All rights reservedActa Cryst. (2014). F70, 21?structural communications??(Fernandes-Alnemri et al., 2009; Burckstummer et al., 2009; Hornung et al., 2009; Roberts et al., 2009). Thus, AIM2 has been shown to play significant roles in host defence against pathogens such as Streptococcus pneumoniae, Listeria monocytogenes, Francisella tularensis, Legionella pneumophila and Mycobacterium tuberculosis (Rathinam et al., 2010; Saiga et al., 2012; Kim et al., 2010; Tsuchiya et al., 2010; Sauer et al., 2010; Fernandes-Alnemri et al., 2010; Jones et al., 2010; Ge et al., 2012; Fang et al., 2011). Even so, high levels of AIM2 and cytosolic DNA have also been located in numerous inflammatory skin ailments (de Koning et al., 2012; Dombrowski et al., 2011).3,4-Diethylhexane-3,4-diol Price In contrast, IFI16 consists of 1 PYD and two HIN domains (HINa and HINb), and has been linked for the formation from the caspase-1-activating inflammasome within the nucleus in response to Kaposi’s sarcomaassociated herpesvirus (Kerur et al.Buy4,5-Dichlorophthalonitrile , 2011).PMID:23695992 The mouse interferon-inducible protein p202 is distinct from other HIN-200 proteins in that it includes only two HIN domains (HINa and HINb) and no PYD domain and has no identified human homologues (Ludlow et al., 2005). Owing for the lack in the PYD domain, p202 cannot bind to ASC via the homotypic PYD YD interaction and is incapable of stimulating inflammatory signalling. Having said that, p202 has been demonstrated to bind DNA effectively (Choubey Gutterman, 1996) and also to interact with mouse Aim2 (inside the following, Aim2 refers to the mouse protein.