The immunoglobulin M molecule: isomeric forms of the monomer subunit.

Abstract

We have devised a novel technique which uses a simple theoretical model to simulate the reduction of immunoglobulin M (IgM) molecules. By fitting the results of the simulated depolymerization to experimental data, we have obtained statistical evidence which suggests that two major isomeric forms of covalently-bonded IgM monomer are liberated when human 19S IgM is reduced with dithiothreitol. The two heavy chains of isomer 1 are linked by two dilsulfide bridges, one in the segment designated the "hinge" region (position 337), the other penultimate to the COOH terminus of the chains (position 575). The half-cystines at position 414, which are free in isomer 1, form an inter-heavy chain bridge in isomer 2. Theoretically, the relative proportions of the two forms of monomer liberated in the reduction depend upon the dithiothreitol concentration, with isomer 2 predominating at higher dithiothreitol concentrations. Although in this paper we have assumed the conventional structure of the IgM molecule, the liberation of isomers depends only upon a symmetrical arrangement of the three types of inter-heavy chain bonds in the cyclic 19S pentamer.