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

Xiaoming Ren, Amy D. Gelinas, Ira Carlowitz, Nebojsa Janjic and Anna Marie Pyle ()
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Xiaoming Ren: Yale University
Amy D. Gelinas: SomaLogic, Inc.
Ira Carlowitz: SomaLogic, Inc.
Nebojsa Janjic: SomaLogic, Inc.
Anna Marie Pyle: Yale University

Nature Communications, 2017, vol. 8, issue 1, 1-13

Abstract: 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.

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00864-2

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DOI: 10.1038/s41467-017-00864-2

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