5uc6

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.