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. 1979 Mar;76(3):1104–1108. doi: 10.1073/pnas.76.3.1104

Structure of the A2m(1) allotype of human IgA—a recombinant molecule

Yasuharu Tsuzukida 1,*, Chi-Chin Wang 1, Frank W Putnam 1,†
PMCID: PMC383197  PMID: 286295

Abstract

The complete amino-acid sequence of the constant (C) region of the α2 heavy chain of a human IgA2 protein of the A2m(1) allotype has been determined. Excluding the hinge region and the carbohydrate content, this α2 allotype differs from the α1 chain in only 14 amino-acid positions; all of these are identical to the A2m(2) allotype of the α2 chain and confer subclass (or isotypic) character on the α2 chains. However, the A2m(2) allotype differs in six positions where A2m(1) and α1 are identical; the first two are just before the hinge and the other four are in the last (CH3) domain. The A2m allotypic character of α2 chains is attributed to several conformational factors in the sequence at positions 211-221, just before the hinge. The isoallotypic determinant shared by α1 chains and the A2m(1) allotype of α2 resides in the identity of their CH3 domains. Thus, the A2m(1) allotype appears to be a hybrid chain that is identical with α1 in the CH3 domain and identical with the A2m(2) α2 chain in the CH1 and CH2 domains and in the hinge, except for the allotypic determinants arising from four structural differences from residues 211-221. The genetic origin of isotypes, allotypes, and isoallotypes of the α chain has involved several events of homologous crossing over and neutral point mutations accumulated late in the evolutionary development of IgA immunoglobulins. Since the crossing over appears to occur between CH2 and CH3, heavy chain domains may be coded for by independent units in embryonic DNA that are analogous to the variable (V) and C segments of light-chain genes.

Keywords: protein structure, amino-acid sequence, genetic markers, isoallotype, immunoglobulins

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Selected References

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