Figure 2. Engineering novel antibody-like proteins. (A) A model of the HIV Envelope spike with gp120 monomers shown in blue and gp41 shown in green and the binding sites for the broadly neutralizing antibodies 4E10 (shown in light green), 2F5 (shown in red), 2G12 (shown in grey), and b12 (also shown in light green). This image is adapted from Burton et al. Nat. Immunol. 5, 233, 2004. (B) This schematic is a representation of an IgG antibody and novel engineered antibody-like proteins. The antigen binding site on the antibody is formed by a portion of the VL and VH domains. Bjorkman and colleagues at Caltech are working on engineering antibody proteins that are smaller than the existing antibodies by only using a part of IgG. The engineered antibodies can contain a single chain with one antigen binding site (scFv); two antigen binding sites of the same specificity (diabody); two antigen binding sites, each with a different specificity (bispecific diabody); or three antigen binding sites with the same specificity (triabody). Engineered antibody proteins that are a combination of three binding sites are expected to bind the antigen more tightly than the natural antibody, which only has two antigen binding sites. Johnson and colleagues are also working on reengineered antibody-like proteins.