Edelman G M, Cunningham B A, Gall W E, Gottlieb P D, Rutishauser U, Waxdal M J
Proc Natl Acad Sci U S A. 1969 May;63(1):78-85. doi: 10.1073/pnas.63.1.78.
The complete amino acid sequence of a human gammaG1 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.
已确定人γG1免疫球蛋白（Eu）的完整氨基酸序列，并确定了所有二硫键的排列方式。将该序列与另一种骨髓瘤蛋白（He）的序列进行比较，结果表明重链和轻链的可变区在长度上同源且相似。重链的恒定部分包含三个同源区域，每个区域大小相似且与轻链的恒定区同源。每个可变区和每个恒定同源区域都包含一个链内二硫键。参与链间键的半胱氨酸都聚集在重链中部的一段十个残基内。这些数据支持这样的假说，即免疫球蛋白是在指定抗原结合功能的V基因和指定抗体分子其他功能的C基因早期分化后通过基因复制进化而来的。因此，每条多肽链可能由两个基因V和C指定，这两个基因融合形成一个单一基因（易位假说）。分子的内部同源性和对称性表明同源区域可能具有相似的三维结构，每个结构都由一个紧凑结构域组成，该结构域至少贡献一个活性位点（结构域假说）。这两种假说都与抗体分子中功能的线性区域差异一致。
