Disulfide bonds within and between proteins are responsible for stabilizing folding and covalent assembly. They are thought to form by an obligatory pathway that leads to a single native structure compatible with secretion. We have previously demonstrated that the intradomain disulfide in the CH1 domain of the Ig γ2b heavy chains was dispensable for secretion [Elkabetz, Y., Argon, Y., Bar-Nun, S., 2005. Cysteines in CH1 underlie retention of unassembled Ig heavy chains. J. Biol. Chem. 280, 14402-14412]. Here we show that the heavy chain-light chain interchain disulfide is also dispensable. γ2b with mutated Cys128, which normally disulfide bonds with the light chain, still assembled with λI light chain into a secretion-competent, tetrameric IgG2b. This assembly comprised of a covalent homo-dimer of mutant heavy chains (C128S2) accompanied non-covalently by a covalent homo-dimer of light chains (λ2). The λ2 homo-dimer formed only upon association with C128S2, through disulfide bonding of the two "orphan" heavy chain-interacting Cys214 in λI. The unique Ig tetramer was secreted efficiently as a functional antibody whose antigen-binding capacity resembled that of normal IgG2b. Therefore, disulfide bonding of Ig manifests considerable plasticity and can generate more than one functional structure that is considered native by the cellular quality control system.
- Disulfide bonds