Antibodies to Sequential and Conformational Determinants

The poor reaction, or total lack of cross reaction, between denatured proteins and antibodies to the same proteins in their native form, was one of the early immunochemical observations (Landsteiner, 1945). Undoubtedly, this phenomenon is due to changes within the conformation of the protein molecule. "Conformation" designates here a particular arrangement of atomic positions of a molecule, which can be achieved without the reorganization of chemical bonds (as in isomerization, tautomerization, inversion) (Schellman and Schellman, 1964). The unique conformation of a native protein is the result of its primary, secondary, tertiary, and—when applicable—quaternary structure. The primary structure is the chemical sequence of amino acids within a polypeptide chain; the secondary structure results from interactions between the polypeptide backbones, usually involving hydrogen bonds(e.g., α-helix, β-structures); the tertiary structure is concerned with intrachain and interchain interactions between amino acid side chains, and includes disulfide bridges; finally, the quaternary structure results from interactions...