Fig. 4. Important charged interactions in the p35–p40 binding interface. (A) R189 (yellow) from p35 helix D projects into a deep, hydrophobic pocket composed of p40 loops 1, 5, 6 (thick) and 3 (thin). A buried hydrogen bonding network (dashes) connects R189 with D290 from p40 through a bound water (red sphere). (B) E181 in p40 is part of a second important charged interaction. Dashed lines indicate hydrogen bonding of p40 E181 with p35 residues R183 and T186. R183 is further stabilized by electrostatic interactions with p35 D108 in helix B.