5UC6

Structural insights into IL-1 alpha recognition by a naphthyl-modified aptamer that mimics IL-1RI Domain III

Summary for 5UC6

• Entry DOI: 10.2210/pdb5uc6/pdb
• Descriptor: Interleukin-1 alpha, DNA (5'-D(*CP*G)-R(P*(85Y))-D(P*GP*AP*G)-R(P*(85Y)P*(85Y))-D(P*A)-R(P*(85Y))-D(P*GP*GP*G)-R(P*(85Y)P*(85Y))-D(P*AP*GP*AP*G)-R(P*(85Y))-D(P*CP*GP*(ATD))-3'), MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: somamer, immune system-dna complex, immune system/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 26646.56

Authors

Ren, X.,Pyle, A. (deposition date: 2016-12-21, release date: 2017-10-11, Last modification date: 2023-10-04)

Primary citation

Ren, X.,Gelinas, A.D.,von Carlowitz, I.,Janjic, N.,Pyle, A.M.
Structural basis for IL-1 alpha recognition by a modified DNA aptamer that specifically inhibits IL-1 alpha signaling.
Nat Commun, 8:810-810, 2017

PubMed 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.

PubMed: 28993621
DOI: 10.1038/s41467-017-00864-2

Experimental method

X-RAY DIFFRACTION (2.1 Å)