Primary structure of human gamma 3 immunoglobulin deletion mutant: gamma 3 heavy-chain disease protein Wis

Abstract

The complete sequence of a gamma 3 heavy-chain disease (HCD) protein Wis is presented. The molecule is a dimer of a 289-residue chain linked by 12 disulfide bonds. Protein Wis has an unusual amino terminus, followed by a deletion of most of the VH domain. After a small stretch homologous to the VC joining region, there is a second deletion which ends at the beginning of the quadruplicated hinge. Two carbohydrate groups are linked to Asn-6 and -140. the molecule has an extra interchain disulfide bridge at position 7 in addition to the 11 normally present in the quadruplicated hinge. The previously noted homology to the gamma 1 heavy chain is striking; from positions 224 to 234, protein Wis resembles gamma 1 Nei [Ponstingl, H., & Hilschmann, N. (1976) Hoppe-Seyler's Z. Physiol. Chem. 357, 1571--1604] except for a serine which replaces Asn at position 227. The results, taken together with studies of other immunoglobulin heavy-chain deletion mutants, support the suggestion that the different domains and interdomain regions of human H chains are coded for by different gene segments and that the deleted proteins reflect alterations in the recombination of different genes and/or the splicing of heterogeneous nuclear messenger ribonucleic acid (hn mRNA).