Framework region

The antibody has a three-dimensional structure with beta pleated sheet and alpha helices. The antibody folds so the variable regions form three loops with the framework regions folded into one another and the CDR regions on the tips of each of these loops in direct contact with the antigen. Individual residues in the framework region can be divided into two categories, depending on whether they are in direct contact with the antigen. Framework residues that come in contact with the antigen are a part of the antibody's binding site, and are located either close in sequence to the CDRs or in close proximity to the CDR when in the folded three dimensional structure. The framework regions are highly conserved regions of the variable portion of the antibody. The evolutionary reason for the conservation of these regions is to support proper folding of the antibody allowing the CDR regions to be stabilized. Folding in FR leads to antibody structure flexibility or rigidity of the binding region of the antibody. == Mutations ==

Mutations in the framework regions of antibodies occur in cells by somatic hypermutation and during affinity maturation of the antibody. In vitro, mutations of FR may occur by natural cause or by exposure to mutagens. Humanized antibody refers to the creation of non-human antibody in vivo and in response to antigen, then the isolation and humanization of the framework and constant regions. It has been discovered that while these antibodies remain relatively intact upon transition, these modifications can also lead to decreased binding affinity in the humanized framework regions and result in improper folding in humans. This observation is believed to be due to the framework region's role in antibody structure. == See also ==