Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling
Year: 2017
Type: article
Abstract: IL-1α 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-1α and inhibits its signaling pathway. By solving the crystal structure of the IL-1α/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-1α/aptamer interface is composed of unusual polar and hydrophobic elements, along with an elaborate hydrogen bonding network that is mediated by sodium ion. IL-1α 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 1α (IL-1α) plays an important role in inflammatory processes. Here the authors use SELEX to generate a modified DNA aptamer which specifically binds IL-1α, present the structure of the IL-1α/aptamer complex and show that this aptamer inhibits the IL-1α signaling pathway.
Source: Nature Communications
Authors: Xiaoming Ren, Amy D. Gelinas, Ira von Carlowitz, Nebojsa Janjic, Anna Marie Pyle
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Howard Hughes Medical Institute, U.S. Department of Energy, National Institutes of Health, Office of Science, National Institute of General Medical Sciences, National Center for Research Resources, Office of Research Infrastructure Programs, National Institutes of Health, Argonne National Laboratory
Awards: G102163711, G107546177, G1313983767, G1505794299, G1664757510, G2101401529, G2164036156, G2287611682, G254657075, G262962599, G2887060908, G3075337988, Pixel Array Detector for X-ray Crystallography, G340565428, G3407338877, G409777406, G498139845, G5106849484, G5201631574, G5607048534, G5915780612, G666778509, G6848031779, G6918803902, G7368700025, NE-CAT Center for Advanced Macromolecular Crystallography, G9000119994, G921583954, G969889393, G993149817
OpenAlex ID: W2762192088