Relationships between the gene and protein structure in human complement component C9.

Relationships between the gene and protein structure in human complement component C9.
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人补体成分C9基因与蛋白质结构的关系。

DOI:
10.1021/bi00417a050
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发表时间:
1988
期刊:
影响因子:
2.9
通讯作者:
Stanley,KK
Stanley,KK
中科院分区:
生物学3区
文献类型:
--
作者:
Marazziti,D;Eggertsen,G;Fey,GH;Stanley,KK

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摘要:人类补体成分C9是一种多结构域蛋白质,其大量的表面形态特征已被确定。我们分析了人类C9基因的外显子-内含子边界,发现剪接位置和蛋白质的表面特征之间有很好的相关性,但与推测的蛋白质结构域结构几乎没有相关性,即使在与低密度脂蛋白(LDL)受体的富含半胱氨酸的序列同源性中也是如此,低密度脂蛋白受体可能是一个独立折叠的结构基序。这是令人惊讶的,因为在低密度脂蛋白受体中,相同的序列精确地被内含子限制,并且已经假设该序列存在于两种蛋白质中,作为外显子改组的结果。我们推断,C9基因外显子-内含子结构的实质性重排必须发生在半胱氨酸富含结构域的交换之前,这可能与产生低密度脂蛋白受体重复序列所需的外显子复制过程有关。(补体成分C9是一个有趣的蛋白质,用于测试外显子-内含子边界与蛋白质结构之间的可能关系。尽管它尚未结晶,但已通过生化(Biesecker等人,1982)和重组DNA实验(Stanley等人,1982;Stanley&Herz,
Revised Manuscript Received May 2, 1988 abstract: Human complement componentC9 is a multidomain protein for which a large number of surface topographical features have been determined. We have analyzed the exon-intron boundaries of the human C9 gene and find a good correlation betweensplice sites and surface features of the proteinbut little correlation with the putative protein domain structure, even in the cysteine-rich sequence homology with the low-density lipoprotein (LDL) receptor which is likely to be an independently folded structural motif. This is surprising because in the LDL receptor the same sequence is precisely bounded by introns, and it has been assumed that this sequence is present in both proteins as a result of exon shuffling. Wededuce that substantial rearrangement of the exon-intron structure of the C9 gene must haveoccurred before the exchange of cysteine-rich domains, possibly linked to the process of exon duplication which was required to generate the repeats in the LDL receptor.(Complement component C9 is an interesting protein in which to test the possible relationships between exon-intron boundaries and protein structure. Although it has notyet been crystallized, a wealth of structural features has been deter-mined by biochemical (Biesecker et al., 1982) and recombinant DNA experiments (Stanley et al., 1982; Stanley & Herz,