Hydrogen bonds network in the IL-4 – IL-4 receptor interface. (a) The hydrogen bond network in cluster III (stippled lines in cyan) between wild type IL-4 and IL-4Rα is shown. Arg85 of IL-4 is H-bonded to residues of IL-4Rα (Asp67 side chain, Asp125 main chain), but several of these H-bonds are mediated via solvent molecules. (b) Model for the interaction of the super-agonist IL-4 T13D with IL-4Rα. The "internal" H-bonds between Asp13 and Arg85 orient the side chain of Arg85 to yield intermolecular H-bonds to the IL-4Rα Asp125 main chain carbonyl. (c) A similar mechanism as in (b) can be drawn for the IL-4 F82D variant when an intramolecular H-bond between IL-4 Asp82 and Arg85 is assumed.