Folding and Oxidation of the Antibody Domain CH3

The non-covalent homodimer formed by the C-terminal domains of the IgG1 heavy chains (CH3) is the simplest naturally occurring model system for studying immunoglobulin folding and assembly. In the native state, the intrachain disulfide bridge, which connects a three-stranded and a four-stranded β-sheet is buried in the hydrophobic core of the protein. Here, we show that the disulfide bridge is not required for folding and association, since the reduced CH3 domain folds to a dimer with defined secondary and tertiary structure. However, the thermodynamic stability of the reduced CH3 dimer is much lower than that of the oxidized state.