5uc6 | pdb_00005uc6

Structural insights into IL-1 alpha recognition by a naphthyl-modified aptamer that mimics IL-1RI Domain III

spinqualitylabelsall models 5uc6, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5uc6 is a 2 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 85Y, ATD, MG, NA, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IL1A_HUMAN Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells. Publication Abstract from PubMed IL-1alpha is an essential cytokine that contributes to inflammatory responses and is implicated in various forms of pathogenesis and cancer. Here we report a naphthyl modified DNA aptamer that specifically binds IL-1alpha and inhibits its signaling pathway. By solving the crystal structure of the IL-1alpha/aptamer, we provide a high-resolution structure of this critical cytokine and we reveal its functional interaction interface with high-affinity ligands. The non-helical aptamer, which represents a highly compact nucleic acid structure, contains a wealth of new conformational features, including an unknown form of G-quadruplex. The IL-1alpha/aptamer interface is composed of unusual polar and hydrophobic elements, along with an elaborate hydrogen bonding network that is mediated by sodium ion. IL-1alpha uses the same interface to interact with both the aptamer and its cognate receptor IL-1RI, thereby suggesting a novel route to immunomodulatory therapeutics.The cytokine interleukin 1alpha (IL-1alpha) plays an important role in inflammatory processes. Here the authors use SELEX to generate a modified DNA aptamer which specifically binds IL-1alpha, present the structure of the IL-1alpha/aptamer complex and show that this aptamer inhibits the IL-1alpha signaling pathway. Structural basis for IL-1alpha recognition by a modified DNA aptamer that specifically inhibits IL-1alpha signaling.,Ren X, Gelinas AD, von Carlowitz I, Janjic N, Pyle AM Nat Commun. 2017 Oct 9;8(1):810. doi: 10.1038/s41467-017-00864-2. PMID:28993621 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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