Conformational significance of the intrachain disulfide linkages in immunoglobulins.

Biophysical studies of intact immunoglobulins, enzymatically derived immunoglobulin subunits, and chemically derived immunoglobulin chains are reported. All the forms studied lacked optical activity associated with the alpha-helix conformation. A dichroism band centered near 217 nm, which has been assigned to the beta-sheet conformation, was present in all subunits that contained at least two covalently linked intrachain disulfide loop regions. This dichroism band could not be detected in Component II, the C-terminal 120 amino acids of the heavy chain. The reduction and alkylation of the intrachain disulfide linkages caused a large conformational change associated with short range interactions. The cleavage of the intrachain disulfide also produced a large change in the environment of two aromatic amino acids, tyrosine and tryptophan. These observations indicate some unique conformational relationships for immunoglobins which may be related to the functional demands placed on this class of macromolecule.