GAMMA-HEAVY CHAIN DISEASE IN MAN - CDNA SEQUENCE SUPPORTS PARTIAL GENE DELETION MODEL
GAMMA-HEAVY CHAIN DISEASE IN MAN - CDNA SEQUENCE SUPPORTS PARTIAL GENE DELETION MODEL
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DOI：
10.1073/pnas.79.10.3260
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
BUXBAUM, JN
中科院分区：
文献类型：
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作者：
ALEXANDER, A;STEINMETZ, M;BUXBAUM, JN
人类γH链疾病（HCD）的特征在于血清中存在短单克隆IG γ。链与L链不相连。虽然大多数HCD蛋白具有内部缺失，但在一些中，缺陷是NH 2末端。OMM γ 3 HCD血清蛋白是后一种类型，其经历了广泛的NH 2-末端缺失，其中序列起始于铰链内。合成OMM蛋白的细胞系允许研究异常分子的生物发生。在体外翻译分离的mRNA产生的蛋白质含有疏水性的NH 2-末端前导序列。在完整细胞中，前体分子被正常加工以产生具有与可变（V）区的开始同源的NH 2末端序列的蛋白质。从OMM mRNA制备的c[互补]DNA的核苷酸序列编码19个氨基酸的前导序列，随后是V区的前15个残基。广泛的内部缺失包括V的其余部分和整个CH 1结构域。紧接着短V区，在cDNA中有整个正常铰链的信息。因此，初级合成产物是内部缺失的分子，其经历合成后降解以产生NH 2末端缺失的血清蛋白。OMM mRNA的结构表明，蛋白质异常是由部分基因缺失引起的，而不是有缺陷的剪接。
Human .gamma. H chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig .gamma. chain unattached to L chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM .gamma.3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein permits the study of the biogenesis of the abnormal molecule. In vitro translation of isolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of c[complementary]DNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues of the V region. An extensive internal deletion encompasses the remainder of the V and the entire CH1 domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein. The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing.