Amino acid substitutions that increase the binding to DSG2. (A) Shown is the amino acid sequence of the Ad3 fiber knob. Beta sheets are indicated by blue lines. Arrows indicate residues within the Ad3 fiber knob which, when mutated, yielded stronger signals in colony blot assays, indicating stronger binding to DSG2. (B) The isosurface of the three knob monomers is colored in gray, pink, and light brown. Mutants involved in DSG2 recognition are shown in the same color as Fig. 1B (yellow, green, blue, and orange), and mutations enhancing the binding are shown in red. (Left) Top view; (right) side view. V239 and Y250 are not exposed at the top, suggesting a structural change in the knob rather than an involvement in direct binding to DSG2. (C) Localization of all mutations that enhance the binding to DSG2. Residues are show in magenta in two knob monomers. The isosurface of one monomer is shown in gray transparency.