Close-up on the hIL-6/hIL-6R binding interface according to our model. hIL-6 is colored grey and hIL-6R is colored yellow. Side chains of residues contributed by hIL-6 are red, whereas those contributed by hIL-6R are green. (A) The hydrophobic and aromatic cluster consisting of Tyr188, Phe248, and Tyr249 from the EF and B′C′ loops of hIL-6R and Phe74 and Phe78 from the AB loop of hIL-6. (B and C) Hydrophilic interactions. (B) Glu296 and Glu297 from the F′G′ loop of hIL-6R interact with Arg179 and Arg182 from the end of the D-helix of hIL-6. (C) Glu254 from the beginning of the C′-β-strand and Glu302 from the F′G′ loop of hIL-6R interact with Arg30 from the A-helix and Arg168 from the D-helix of hIL-6, respectively.