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小鼠Cμ重链免疫球蛋白基因片段包含三个分隔结构域的间隔序列。

Mouse Cmu heavy chain immunoglobulin gene segment contains three intervening sequences separating domains.

作者信息

Calame K, Rogers J, Early P, Davis M, Livant D, Wall R, Hood L

出版信息

Nature. 1980 Apr 3;284(5755):452-5. doi: 10.1038/284452a0.

Abstract

The IgM molecule is composed of subunits made up of two light chain and two heavy chain (mu) polypeptides. The mu chain is encoded by several gene segments--variable (V), joining (J) and constant (Cmu). The Cmu gene segment is of particular interest for several reasons. First, the mu chain must exist in two very different environments--as an integral membrane protein in receptor IgM molecules (micrometer) and as soluble serum protein in IgM molecules into the blood (mus). Second, the Cmu region in mus is composed of four homology units or domains (Cmu1, Cmu2, Cmu3 and Cmu4) of approximately 110 amino acid residues plus a C-terminal tail of 19 residues. We asked two questions concerning the organisation of the Cmu gene segment. (1) Are the homology units separated by intervening DNA sequences as has been reported for alpha (ref. 5), gamma 1 (ref. 6) and gamma 2b (ref. 7) heavy chain genes? (2) Is the C-terminal tail separated from the Cmu4 domain by an intervening DNA sequence? If so, DNA rearrangements or RNA splicing could generate hydrophilic and hydrophobic C-terminal tails for the mus and micrometer polypeptides, respectively. We demonstrate here that intervening DNA sequences separate each of the four coding regions for Cmu domains, and that the coding regions for the Cmu4 domains and the C-terminal tail are directly contiguous.

摘要

IgM分子由亚基组成,这些亚基由两条轻链和两条重链(μ)多肽构成。μ链由几个基因片段编码,即可变区(V)、连接区(J)和恒定区(Cμ)。Cμ基因片段因多种原因而备受关注。首先,μ链必须存在于两种截然不同的环境中:作为受体IgM分子(μm)中的整合膜蛋白,以及作为血液中IgM分子的可溶性血清蛋白(μs)。其次,μs中的Cμ区域由四个同源单位或结构域(Cμ1、Cμ2、Cμ3和Cμ4)组成,每个结构域约有110个氨基酸残基,外加一个19个残基的C末端尾巴。我们针对Cμ基因片段的组织提出了两个问题。(1)同源单位是否像已报道的α(参考文献5)、γ1(参考文献6)和γ2b(参考文献7)重链基因那样被间隔DNA序列隔开?(2)C末端尾巴是否通过间隔DNA序列与Cμ4结构域分开?如果是这样,DNA重排或RNA剪接可能分别为μs和μm多肽产生亲水和疏水的C末端尾巴。我们在此证明,间隔DNA序列将Cμ结构域的四个编码区域彼此隔开,并且Cμ4结构域和C末端尾巴的编码区域直接相邻。

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