Three-dimensional structure of immunoglobulins

The three-dimensional structure of several immunoglobulins and their fragments have been determined by single crystal x-ray diffraction methods. These studies have shown that immunoglobulins are multimeric proteins consisting of globular subunits arranged in pairs. These subunits of the L and H chains contain homologous amino acid sequences ('homology regions') about 110 amino acids long, and share a common pattern of three-dimensional chain folding ('immunoglobulin-fold'). Studies on the primary and tertiary structure of immunoglobulins substantiate the postulate that the different homology subunits arose during evolution by a mechanism of gene duplication and diversification. This mechanism provided the structural basis for the different functions of antibody molecules. The evolutionary mechanism did not alter the overall folding pattern of the subunits. However, within an immunoglobulin molecule the subunits pair in three different types of geometrical arrangement. These different pairing schemes are determined by amino acid substitutions in the β-sheets of the subunits. The major amino acid differences between immunoglobulin of the same class and of the same animal species occur in the loops connecting the β-pleated sheet strands. Starting from the known structure of immunoglobulin fragments some attempts have been made to predict the conformation of the combining site of other immunoglobulins based solely on their amino acid sequences. Trial models have been derived by this general procedure but there is not yet enough information to evaluate their accuracy. The determination of three-dimensional structures of additional immunoglobulin-combining sites will be necessary to ascertain the ultimate potential of this approach. The studies on the three-dimensional structures of immunoglobulins and their fragments, reviewed below, have provided invaluable information for the understanding of the structural basis of antibody function. Further studies will be needed, however, to complete our knowledge of the chemical basis of antibody specificity and to understand the triggering and the structural localization of effector functions.