The thiol groups of mouse immunoglobulin A. Incomplete formation of the Cα 1-domain disulphide bridge

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Abstract
The BALB/c IgA myeloma protein M167 contained on average 5.7 free SH groups per IgA dimer. These groups were preponderantly on the heavy chains and comprised 2 distinct populations: 3.3 exposed SH groups per dimer in the Fc regions, and 2.4 buried SH groups per dimer in the Fd region, detectable only after denaturation. To locate the cysteine residues involved, labeled peptides were purified from thermolysin digests of radioalkylated IgA by high-performance liquid chromatography. From the amino acid compositions of the peptides, the exposed thiol groups were assigned to Cys-307 in the C.alpha.2 domain, which thus existed in the reduced form to an extent exceeding 80%. This residue may allow attachment of secretory component to dimer IgA in the mouse to proceed via thiol-disulfide exchange. The buried thiol groups were assigned to Cys-150 and Cys-208, in the C.alpha.1 domain, each being in the reduced form to the extent of .apprx. 30%. This pair of residues would normally give rise to the characteristic intradomain disulfide bridge. It appears that disulfide formation is not a crucial event during folding of the C.alpha.1 domain in IgA biosynthesis. The sequence in the region 140-151 was re-investigated, and residue 142 was shown to be serine, not cysteine, helping explain the lack of heavy-chain-light chain bonding in BALB/c mouse IgA. A disulfide-bond model for mouse IgA is proposed on the basis of these assignments and other features of the mouse .alpha.-chain sequence.