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

Structure of the A2m(1) allotype of human IgA--a recombinant molecule.
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人类 IgA A2m(1) 同种异型的结构——重组分子。

DOI:
10.1073/pnas.76.3.1104
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发表时间:
1979
影响因子:
11.1
通讯作者:
F. Putnam
F. Putnam
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Y. Tsuzukida;C. Wang;F. Putnam

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被引文献

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A2m(1) 同种异型人 IgA2 蛋白的 α2 重链恒定 (C) 区的完整氨基酸序列已确定。排除铰链区和碳水化合物含量,这种 α2 同种异型与 α1 链仅在 14 个氨基酸位置上有所不同;所有这些都与 alpha2 链的 A2m(2) 同种异型相同,并赋予 alpha2 链子类(或同种型)特征。然而,A2m(2) 同种异型在 A2m(1) 和 alpha1 相同的六个位置上有所不同;前两个位于铰链之前,其他四个位于最后一个 (C(H)3) 域中。 α2链的A2m同种异型特征归因于序列中位于铰链之前的位置211-221处的几个构象因素。 α1 链和 α2 的 A2m(1) 同种异型共享的同种异型决定簇存在于它们的 C(H)3 结构域的同一性中。因此,A2m(1)同种异型似乎是一条杂合链,其与C(H)3结构域中的α1相同,并且与C(H)1和C(H)2结构域中以及铰链中的A2m(2)α2链相同,除了由残基211-221的四个结构差异产生的同种异型决定簇之外。 α链的同种型、同种异型和同种同种异型的遗传起源涉及在IgA免疫球蛋白进化发展后期积累的多个同源交换和中性点突变事件。由于交换似乎发生在 C(H)2 和 C(H)3 之间,因此重链结构域可能由胚胎 DNA 中的独立单元编码,类似于轻链基因的可变 (V) 和 C 片段。
The complete amino-acid sequence of the constant (C) region of the alpha2 heavy chain of a human IgA2 protein of the A2m(1) allotype has been determined. Excluding the hinge region and the carbohydrate content, this alpha2 allotype differs from the alpha1 chain in only 14 amino-acid positions; all of these are identical to the A2m(2) allotype of the alpha2 chain and confer subclass (or isotypic) character on the alpha2 chains. However, the A2m(2) allotype differs in six positions where A2m(1) and alpha1 are identical; the first two are just before the hinge and the other four are in the last (C(H)3) domain. The A2m allotypic character of alpha2 chains is attributed to several conformational factors in the sequence at positions 211-221, just before the hinge. The isoallotypic determinant shared by alpha1 chains and the A2m(1) allotype of alpha2 resides in the identity of their C(H)3 domains. Thus, the A2m(1) allotype appears to be a hybrid chain that is identical with alpha1 in the C(H)3 domain and identical with the A2m(2) alpha2 chain in the C(H)1 and C(H)2 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 alpha 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 C(H)2 and C(H)3, 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.