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Proc Natl Acad Sci U S A. May 1969; 63(1): 78–85.
PMCID: PMC534037

THE COVALENT STRUCTURE OF AN ENTIRE γG IMMUNOGLOBULIN MOLECULE*

Abstract

The complete amino acid sequence of a human γG1 immunoglobulin (Eu) has been determined and the arrangement of all of the disulfide bonds has been established. Comparison of the sequence with that of another myeloma protein (He) suggests that the variable regions of heavy and light chains are homologous and similar in length. The constant portion of the heavy chain contains three homology regions each of which is similar in size and homologous to the constant region of the light chain. Each variable region and each constant homology region contains one intrachain disulfide bond. The half-cystines participating in the interchain bonds are all clustered within a stretch of ten residues at the middle of the heavy chains.

These data support the hypothesis that immunoglobulins evolved by gene duplication after early divergence of V genes, which specified antigen-binding functions, and C genes, which specified other functions of antibody molecules. Each polypeptide chain may therefore be specified by two genes, V and C, which are fused to form a single gene (translocation hypothesis). The internal homologies and symmetry of the molecule suggest that homology regions may have similar three-dimensional structures each consisting of a compact domain which contributes to at least one active site (domain hypothesis). Both hypotheses are in accord with the linear regional differential of function in antibody molecules.

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Selected References

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