THE APOLIPOPROTEIN MULTIGENE FAMILY - STRUCTURE, EXPRESSION, EVOLUTION, AND MOLECULAR-GENETICS
THE APOLIPOPROTEIN MULTIGENE FAMILY - STRUCTURE, EXPRESSION, EVOLUTION, AND MOLECULAR-GENETICS
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DOI：
10.1007/bf01717324
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发表时间：
1989-02-15
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影响因子：
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通讯作者：
CHAN, L
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作者：
CHAN, L
血浆载脂蛋白可分为两个亚组：可溶性载脂蛋白包括载脂蛋白（apo）A-I、A-II、A-IV、C-I、C-II、C-III和E，以及apoB包括apoB-100和apoB-48。可溶性载脂蛋白具有非常相似的基因组结构，每个载脂蛋白在相同位置共有三个内含子； apoA-IV 是一个例外，因为它失去了第一个内含子。使用外显子/内含子连接作为参考点，我们可以获得所有可溶性载脂蛋白基因的编码区的比对。基因的成熟肽区域几乎完全由 11 个密码子的串联重复组成。由外显子 3 编码的成熟肽区域部分包含 33 个密码子的共同块，而由外显子 4 编码的部分包含数量更多的 11 个密码子内部重复。基于各种序列的同源性程度以及这些基因的内部重复模式，已经提出了可溶性载脂蛋白基因的进化树。 ApoB-100 与可溶性载脂蛋白有很大不同。它是最大的载脂蛋白，含有 4536 个氨基酸残基。 apoB-100 中鉴定出两种类型的内部重复序列：两亲性 α-螺旋重复序列和具有高 β-折叠含量的含脯氨酸重复序列。 apoB基因包含29个外显子和28个内含子。它与可溶性载脂蛋白基因的进化关系尚不清楚。 apoB 基因的 3' 端包含一个可变数量的串联 12-16 碱基对重复区域。我们应用聚合酶链反应技术来表征这个高度多态性基因座。相同的技术可用于准确地键入其他可变数量的串联重复基因座。最后，apoB-48 被证明是涉及肠 mRNA 的 RNA 编辑机制的产物，该肠 mRNA 具有框内 UAA 终止密码子，该终止密码子是由于 apoB-100 mRNA 中编码 Gln-2153 的密码子 CAA 发生 C→U 变化而产生的。使用分子方法进行载脂蛋白合成、结构和遗传分析，我们生成了对我们理解脂蛋白代谢很重要的信息；我们还发现了与一般细胞和分子生物学以及分子进化相关的意想不到的实验结果。
The plasma apolipoproteins can be classified into two subgroups: the soluble apolipoproteins including apolipoprotein (apo) A-I, A-II, A-IV, C-I, C-II, C-III, and E, and the apoBs including apoB-100 and apoB-48. The soluble apolipoproteins have very similar genomic structures, each having a total of three introns at the same locations; apoA-IV is an exception in that it has lost its first intron. Using the exon/intron junctions as reference points, we can obtain an alignment of the coding regions of all the soluble apolipoprotein genes. The mature peptide regions of the genes are almost completely made up of tandem repeats of 11 codons. The part of mature peptide region encoded by exon 3 contains a common block of 33 codons, whereas the part encoded by exon 4 contains a much more variable number of internal repeats of 11 codons. On the basis of the degree of homology of the various sequences, and the pattern of the internal repeats in these genes, an evolutionary tree has been proposed for the soluble apolipoprotein genes. ApoB-100 differs considerably from the soluble apolipoproteins. It is the largest apolipoprotein containing 4536 amino acid residues. Two types of internal repeats are identified in apoB-100: amphipathic α-helical repeats and proline-containing repeats with high β-sheet content. The apoB gene contains 29 exons and 28 introns. Its evolutionary relationship to the soluble apolipoprotein genes is unclear. The 3′ end of the apoB gene contains a region of variable number of tandem 12–16-base pair repeats. We have applied the polymerase chain reaction technique to characterize this highly polymorphic locus. The same technique can be used to accurately type other variable number of tandem repeats loci. Finally, apoB-48 was shown to be the product of an RNA editing mechanism involving an intestinal mRNA that has an in-frame UAA stop codon resulting from a C→U change in the codon CAA encoding Gln-2153 in apoB-100 mRNA. Using a molecular approach to apolipoprotein synthesis, structure and genetic analysis, we have generated information important to our understanding of lipoprotein metabolism; we also uncovered unexpected experimental results that are relevant to general cell and molecular biology and molecular evolution.