"Alpha chain disease" protein def: internal deletion of a human immunoglobulin A1 heavy chain

Protein Def is a human alpha chain disease protein related to alpha1 immunoglobulin heavy chain. The molecular weight of the polypeptide portion of the monomeric molecule is 29,300, which is a little greater than half of a normal alpha1 chain. The NH(2)-terminal of the polypeptide is heterogenous and, after a short segment corresponding to the variable region, displays a gap which comprises the C(H)1 constant domain. Normal synthesis resumes at a valine residue in the hinge region just before a segment which contains a partially duplicated fragment and the interheavy disulfide bonds. From there on, the molecule is apparently normal. Protein Def is therefore synthesized as an internally deleted alpha1 heavy chain, followed by postsynthetic amino-terminal proteolysis. It is postulated that codon(s) specifying valine at the hinge region may be a recognition site for reinitiating synthesis after internal gaps equivalent to position 216 in gamma chain disease proteins.