HUMAN-SERUM AMYLOID-A - 3 HEPATIC MESSENGER-RNAS AND THE CORRESPONDING PROTEINS IN ONE PERSON
HUMAN-SERUM AMYLOID-A - 3 HEPATIC MESSENGER-RNAS AND THE CORRESPONDING PROTEINS IN ONE PERSON
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DOI：
10.1172/jci113779
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发表时间：
1988-11-01
影响因子：
15.9
通讯作者：
BENSON, MD
中科院分区：
文献类型：
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作者：
KLUVEBECKERMAN, B;DWULET, FE;BENSON, MD
血清淀粉样蛋白 A (SAA) 是人类和大多数其他哺乳动物的主要急性期蛋白。此外，它是反应性淀粉样原纤维主要蛋白质成分的血清前体。序列分析已鉴定出人类 SAA 和淀粉样 A 蛋白 (AA) 的多种多态性形式，但人类中编码 SAA 的基因数量问题尚未得到解决。此外，没有足够的数据来预测一种形式的 SAA 是否容易形成淀粉样原纤维。在本研究中，从一个人的血浆中分离出三种不同的 SAA 蛋白，并对其进行了完整测序。虽然两种 SAA 形式（SAA2.alpha. 和 SAA2.beta.）仅在位置 71 处彼此不同，但它们分别在其他 7 个和 8 个位置处与最丰富的形式 (SAA1) 不同。对来自该个体肝脏文库的 cDNA 进行核苷酸测序，鉴定出编码这些蛋白质的所有三种 mRNA，并证明：(a) 经常报道的 SAA 蛋白质氨基末端缺乏精氨酸必定是该蛋白质的蛋白水解加工造成的； (b)第71位涉及组氨酸和精氨酸的多态性存在于DNA水平，因此不是由翻译水平的事件引起； (c) 至少有两个编码人类 SAA 的基因。将这些数据与已发表的 SAA 和 AA 蛋白序列进行比较，可能有助于识别 SAA 的遗传决定形式，这些形式容易形成反应性淀粉样原纤维。
Serum amyloid A protein (SAA) is a major acute-phase protein in humans and most other mammals. In addition, it is the serum precursor of the major protein constituent of reactive amyloid fibrils. Sequence analyses have identified a number of polymorphic forms of human SAA and amyloid A protein (AA), but the question of the number of genes encoding SAA in the human has not been addressed. In addition, there are insufficient data to predict whether one form of SAA predisposes to amyloid fibril formation. In the present study three separate SAA proteins have been isolated from the plasma of one individual and completely sequenced. While two of the SAA forms (SAA2.alpha. and SAA2.beta.) differ from each other only at position 71, they differ from the most abundant form (SAA1) at seven and eight other positions, respectively. Nucleotide sequenching of cDNAs from a liver library of this individual identified all three mRNAs coding for these proteins and proved that: (a) the often-reported absence of arginine at the amino terminus of SAA proteins must result from proteolytic processing of the protein; (b) the polymorphism involving histidine and arginine at position 71 is present at the DNA level and therefore is not due to an event at the translational level; (c) there are at least two genes coding for human SAA. Comparison of these data to published sequences of SAA and AA proteins may help in identifying genetically determined forms at SAA which predispose to reactive amyloid fibril formation.