Ciated speck-like protein containing a caspaserecruitment domain). ASC can further recruit
Ciated speck-like protein containing a caspaserecruitment domain). ASC can additional recruit the effector enzyme procaspase-1, p38β Purity & Documentation resulting within the formation with the large signalling complex inflammasome as well as the activation of inflammatory responsesdoi:ten.1107/S2053230X1303135X# 2014 Global Union of Crystallography All rights reservedActa Cryst. (2014). F70, 21structural communications(Fernandes-Alnemri et al., 2009; Burckstummer et al., 2009; Hornung et al., 2009; Roberts et al., 2009). Therefore, AIM2 has been proven to perform substantial roles in host defence against pathogens for instance 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). Having said that, higher ranges of AIM2 and cytosolic DNA have also been found in a number of inflammatory skin diseases (de Koning et al., 2012; Dombrowski et al., 2011). In contrast, IFI16 consists of one PYD and two HIN domains (HINa and HINb), and has been linked to the formation on the caspase-1-activating inflammasome in the nucleus in response to Kaposi’s sarcomaassociated herpesvirus (Kerur et al., 2011). The mouse interferon-inducible protein p202 is distinct from other HIN-200 proteins in that it contains only two HIN domains (HINa and HINb) and no PYD domain and has no identified human homologues (Ludlow et al., 2005). Owing to the lack from the PYD domain, p202 cannot bind to ASC through the homotypic PYD YD interaction and is incapable of stimulating inflammatory signalling. On the other hand, p202 is demonstrated to bind DNA efficiently (Choubey Gutterman, 1996) and also to interact with mouse Aim2 (within the following, Aim2 refers towards the mouse protein and AIM2 denotes the human protein) in cytosol (Choubey et al., 2000). These properties have recently been linked towards the inhibitory impact of p202 on Aim2 inflammasome activation (Roberts et al., 2009). Nevertheless, the molecular mechanism by which p202 represses Aim2-dependent inflammatory signalling remains elusive. Recently, structural studies have validated the existence of two oligonucleotide/oligosaccharide-binding (OB) fold subdomains inside every single HIN domain and have uncovered the molecular mechanisms of DNA recognition through the HIN domains of AIM2, IFI16 and p202 (Jin et al., 2012; Yin et al., 2013; Ru et al., 2013; Liao et al., 2011). Right here, we established the crystal structure on the p202 HINa domain in complex with 20 bp double-stranded DNA, in which two p202 HINa molecules bind tandemly towards the main groove of dsDNA. The p202 HINa domain binds DNA within a diverse method in the HIN domains of AIM2/Aim2 and IFI16. Working with these results and Adenosine A3 receptor (A3R) Inhibitor Source reported biochemical and structural data, we propose a conceivable model for your interaction of full-length p202 with dsDNA, which sheds light around the inhibitory part of p202 on Aim2 function.TableData-collection and refinement statistics.The data set was collected from a single crystal. Values in parentheses are to the highest resolution shell. Information assortment Room group Unit-cell parameters (A, ) Resolution (A) No. of unique reflections Multiplicity Completeness ( ) hI/(I)i Rmerge ( ) Refinement Resolution (A) Rwork/Rfree ( ) No. of atoms Protein DNA Water Average B factors (A2) Wilson B element Protein DNA Water R.m.s. deviations Bond lengths (A) Bond angles ( ) Ramac.