Robinson E A, Appella E
Proc Natl Acad Sci U S A. 1980 Aug;77(8):4909-13. doi: 10.1073/pnas.77.8.4909.
The complete amino acid sequence of the 432-residue heavy (alpha) chain of mouse myeloma MOPC 511 has been determined. The variable region of the alpha chain of IgA 511, a phosphocholine-binding protein, is highly homologous to that of the other phosphocholine-binding immunoglobulins. Comparison of the 511 alpha chain constant region with that of other mouse and human heavy chains shows that sequence divain. The CH3 domain disulfide bridge of the 511 alpha chain, for example, consists of only 28 amino acid residues compared to 60 residues for other chains and domains. Sequence divergences are alsos apparent at the CH2/CH3 domain boundary, an area where a number of frameshift mutations have occurred. One mutant, mouse IgA 47A, lacks the entire CH3 domain. Comparison of the 511 alppha chain with the 47A alpha chain reveals two noncconservative amino acid changes at the COOH terminus of the 47A chain, Ser-Gln for VAl-Thr in the 511 chain. These changes and the deletion of the CH3 domain can be explained by a single genetic event--namely, a frameshift mutation followed by premature chain termination. The remainder of the 47A constant region, including the hinge region, is identical to the 511 alpha chain, except for two conservative changes in the CH1 domain: serine-126 and theonine-197 in the 511 alpha chain are both replaced by alanine in the 47A chain.
已确定小鼠骨髓瘤MOPC 511的432个残基重(α)链的完整氨基酸序列。IgA 511是一种磷酸胆碱结合蛋白,其α链的可变区与其他磷酸胆碱结合免疫球蛋白的可变区高度同源。将511α链恒定区与其他小鼠和人类重链的恒定区进行比较,发现序列存在差异。例如,511α链的CH3结构域二硫键仅由28个氨基酸残基组成,而其他链和结构域为60个残基。在CH2/CH3结构域边界也明显存在序列差异,该区域发生了许多移码突变。一个突变体,小鼠IgA 47A,缺失整个CH3结构域。将511α链与47Aα链进行比较,发现在47A链的COOH末端有两个非保守氨基酸变化,511链中的Val-Thr变为47A链中的Ser-Gln。这些变化以及CH3结构域的缺失可以用一个单一的遗传事件来解释,即移码突变后紧接着链的过早终止。47A恒定区的其余部分,包括铰链区,与511α链相同,除了CH1结构域中的两个保守变化:511α链中的丝氨酸-126和苏氨酸-197在47A链中均被丙氨酸取代。