Fab domain

Antibody consists of fragment ab (Fab) domain that binds to the antigen and fragment c (Fc) domain that recruits immune effector cells. Accordingly, receptors for the constant region (Fc) of antibodies provide critical links between the cellular and humoral parts of the immune system (6). 

Certain orientations may make a specific site on the protein inaccessible to ligand, substrate, or antigen. For example, consider the adsorptive immobilization of a specific IgG for a solid-phase immunoassay. The procedure will be optimal if the Fab domains are free to bind antigen (Figs. 1 and 16). 

Figure 4.30. Antibody Structure. (A) IgG antibodies consist of four chains, two heavy chains (blue) and two light chains (red), linked by disulfide bonds. The heavy and light chains come together to form Fab domains, which have the antigen-binding sites at the ends. The two heavy chains form the Fc domain. The Fab domains are linked to the Fc domain by flexible linkers. (B) A more schematic representation of an IgG molecule.

Figure 3.28 Antigen-antibody interactions. A protein antigen, in this case lysozyme, binds to the end of an Fab domain of an antibody. Notice that the end of the antibody and the antigen have complementary shapes, allowing a large amount of surface to be buried on binding. [Drawn from 3HFL.pdb.]...

Fig. 4. Conformational diversity in an antibody esterase. Whether the amino acid belongs to a heavy or light chain is indicated with the letter H or L before the sequence number, a) Superposition of the germ-line Fab-hapten complex (Fab=antigen-binding fragment of an antibody purple) and the affinity-matured Fab-hapten complex (red). Somatically mutated residues (X Y) are shown in green, b) Superposition of the structures of the germ-line Fab domain...

Carrasco, B., de la Torre, J. G., Byron, O., King, D., Walters, C., Jones, S., and Harding, S. H., Novel size-independent modeling of the dilute solution conformation of the immunoglobnhn IgG Fab Domain using Solpro and Ellipse, Biophys. J., 77, 2902-2910 (1999). 

Figure 8.11b. The Fa and Fab domains of immunoglobuline. Adapted from C. Brandenand J.Toozel .

Multiple groups have taken an alternative approach to this problem by using recombinant techniques to add an additional antigen recognition site to both Fab domains of an IgG. This addition allows for simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Wu et al. report that such an approach provides therapeutic proteins with high potential of success for the treatment of human diseases. ... 

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