Fig. 4. Crystal structure of the hIL-1β/(S)-2 complex.

a Superposition of the hIL-1β/(S)-2 complex (cyan) with hIL-1β as observed in the ternary signaling complex with IL-1R1 and IL-1RAcP (salmon; PDB: 4DEP;³¹ the receptor chains are not shown). The antagonist binds to a cryptic pocket formed by residues of the N-terminus, loop β4–5, and loop β7–8. H-bonded interactions between (S)-2 and IL-1β are shown with dashed lines. b Same overlay with IL-1R1 shown as a gray ribbon. c Close-up view of the region highlighted by the dotted square in (b). The orientation was changed to better show the displacement of loop β4–5 (residues 47–55) by up to 11 Å upon compound binding. The antagonist-bound conformation (cyan) is incompatible with proper engagement of the cytokine with domain 3 of IL-1R1.