Structural basis for IL-1? recognition by a modified DNA aptamer that specifically inhibits IL-1? signaling.

ABSTRACT: IL-1? 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-1? and inhibits its signaling pathway. By solving the crystal structure of the IL-1?/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-1?/aptamer interface is composed of unusual polar and hydrophobic elements, along with an elaborate hydrogen bonding network that is mediated by sodium ion. IL-1? 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 1? (IL-1?) plays an important role in inflammatory processes. Here the authors use SELEX to generate a modified DNA aptamer which specifically binds IL-1?, present the structure of the IL-1?/aptamer complex and show that this aptamer inhibits the IL-1? signaling pathway.

SUBMITTER: Ren X 

PROVIDER: S-EPMC5634487 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature