4p0k | pdb_00004p0k

Crystal Structure of Double Loop-Swapped Interleukin-36Ra

spinqualitylabelsall models 4p0k, resolution 1.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p0k is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease I36RA_HUMAN Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. The disease is caused by mutations affecting the gene represented in this entry. Function IL36G_HUMAN Function as an agonist of NF-kappa B activation through the orphan IL-1-receptor-related protein 2/IL1RL2. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.I36RA_HUMAN Is a highly and a specific antagonist of the IL-1 receptor-related protein 2/IL1RL2-mediated response to interleukin IL36G. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response. Publication Abstract from PubMed The IL-1 family consists of 11 cytokines that control a complex network of proinflammatory signals critical for regulating immune responses to infections. They also play a central role in numerous chronic inflammatory disorders. Accordingly, inhibiting the activities of these cytokines is an important therapeutic strategy for treating autoimmune diseases and lymphomas. Agonist cytokines in the IL-1 family activate signaling by binding their cognate receptor and then recruiting a receptor accessory protein. Conversely, antagonist cytokines bind their cognate receptor but prohibit recruitment of receptor accessory protein, which precludes functional signaling complexes. The IL-36 subfamily of cytokines is the most diverse, including three agonists and at least one antagonist, and is the least well-characterized group within this family. Signaling through the IL-36 receptor directly stimulates dendritic cells and primes naive CD4 T cells for Th1 responses. Appropriately balanced IL-36 signaling is a critical determinant of skin and lung health. IL-36 signaling has been presumed to function analogously to IL-1 signaling. In this study, we have defined molecular determinants of agonist and antagonist signaling through the IL-36 receptor. We present the crystal structure of IL-36gamma, which, to our knowledge, is the first reported structure of an IL-36 agonist. Using this structure as a guide, we designed a comprehensive series of IL-36 agonist/antagonist chimeric proteins for which we measured binding to the IL-36 receptor/IL-1 receptor accessory protein complex and functional activation and inhibition of signaling. Our data reveal how the fine specificity of IL-36 signaling is distinct from that of IL-1. Molecular Determinants of Agonist and Antagonist Signaling through the IL-36 Receptor.,Gunther S, Sundberg EJ J Immunol. 2014 Jun 16. pii: 1400538. PMID:24935927 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin receptor antagonist

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