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

Nat Commun. 2017 Oct 9;8(1):810. doi: 10.1038/s41467-017-00864-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / metabolism
  • Aptamers, Nucleotide / pharmacology*
  • Binding, Competitive
  • Crystallography, X-Ray
  • Deoxyuridine / chemistry
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Interleukin-1alpha / chemistry*
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism*
  • Interleukin-1beta / metabolism
  • Models, Molecular
  • Receptors, Interleukin-1 / metabolism
  • SELEX Aptamer Technique
  • Signal Transduction / drug effects


  • Aptamers, Nucleotide
  • IL1A protein, human
  • Interleukin-1alpha
  • Interleukin-1beta
  • Receptors, Interleukin-1
  • Deoxyuridine