2l6a

Three-dimensional structure of the N-terminal effector PYRIN domain of NLRP12

spinqualitylabelsall models 2l6a Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2l6a is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease NAL12_HUMAN NLRP12-associated hereditary periodic fever syndrome. The disease is caused by mutations affecting the gene represented in this entry. Function NAL12_HUMAN May mediate activation of CASP1 via ASC and promote activation of NF-kappa-B via IKK. Publication Abstract from PubMed The initial line of defense against infection is sustained by the innate immune system. Together, membrane-bound Toll-like receptors and cytosolic nucleotide-binding domain and leucine-rich repeat-containing receptors (NLR) play key roles in the innate immune response by detecting bacterial and viral invaders as well as endogenous stress signals. NLRs are multi-domain proteins with varying N-terminal effector domains that are responsible for regulating downstream signaling events. Here, we report the structure and dynamics of the N-terminal pyrin domain of NLRP12 (NLRP12 PYD) determined using NMR spectroscopy. NLRP12 is a non-inflammasome NLR that has been implicated in the regulation of Toll-like receptor-dependent nuclear factor-kappaB activation. NLRP12 PYD adopts a typical six-helical bundle death domain fold. By direct comparison with other PYD structures, we identified hydrophobic residues that are essential for the stable fold of the NLRP PYD family. In addition, we report the first in vitro confirmed non-homotypic PYD interaction between NLRP12 PYD and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling. Interestingly, all residues that participate in this protein:protein interaction are confined to the alpha2-alpha3 surface, a region of NLRP12 PYD that differs most between currently reported NLRP PYD structures. Finally, we experimentally highlight a significant role for tryptophan 45 in the interaction between NLRP12 PYD and the FAF-1 UBA domain. The NLRP12 Pyrin Domain: Structure, Dynamics, and Functional Insights.,Pinheiro AS, Eibl C, Ekman-Vural Z, Schwarzenbacher R, Peti W J Mol Biol. 2011 Nov 4;413(4):790-803. Epub 2011 Sep 28. PMID:21978668 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pyrin domain

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