SNAP output for PDB entry 5uc6 [SNAP web server]

PDB-id

5uc6; SNAP-derived features in text and JSON formats; DNAproDB

Class

immune system-DNA

Method

X-ray (2.1 Å)

Summary

Structural insights into il-1 alpha recognition by a naphthyl-modified aptamer that mimics il-1ri domain iii

Reference

Ren X, Gelinas AD, von Carlowitz I, Janjic N, Pyle AM (2017): "Structural basis for IL-1 alpha recognition by a modified DNA aptamer that specifically inhibits IL-1 alpha signaling." Nat Commun, 8, 810. doi: 10.1038/s41467-017-00864-2.

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.