Folding, association, and interactions of domains in the antibody molecule.

The domain model of immunoglobulin (Ig) structure (Edelman and Gall 1969) implies independent folding and localized function for each domain. It is clear, however, that the function of the intact antibody molecule is due to noncovalent interactions between domains. These interactions may take place between neighboring domains on the same chain (cis interaction) as well as between domains on separate chains (trans interaction). Strong trans interactions occur between VL and VH, CL and CH1 in Fab, and between the CH3 domains in Fc. It seems that there is no interaction between CH2 domains since the divalent fragment Facb dissociates into monovalent fragments after reduction of the inter-heavy-chain disulfide bonds (Press 1975). Cis interactions are present between VL and CL, VH and CH1, and between CH2 and CH3. It appears that the CH2-CH3 interactions are weaker than those of VL-CL and VH-CH1 since it is possible to prepare Facb from rabbit...