NUCLEOTIDE-SEQUENCE OF A CDNA CLONE ENCODING HUMAN PREPROINSULIN
NUCLEOTIDE-SEQUENCE OF A CDNA CLONE ENCODING HUMAN PREPROINSULIN
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DOI：
10.1038/282525a0
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发表时间：
1979-01-01
期刊：
影响因子：
64.8
通讯作者：
RUTTER, WJ
中科院分区：
文献类型：
--
作者：
BELL, GI;SWAIN, WF;RUTTER, WJ
胰岛素由两条多肽链组成，A（21个氨基酸）和B（30个氨基酸），由二硫键连接。两条链都来源于一个前体，胰岛素原，它包括a链和B链之间的连接肽(C)，在胰腺B细胞分泌胰岛素之前被切除1。与高度保守的A和B序列（1 - 3）相比，c肽在物种之间存在差异，这与它在胰岛素合成中发挥纯粹的结构功能的理论是一致的。在胰岛素mRNA的体外翻译过程中，主要产物是一个较大的肽，在n端含有大约25个额外的残基（胰岛素前原）。在转运到内质网的过程中，前肽被裂解留下胰岛素原，并被认为是具体指导这一过程的8。利用自动氨基酸序列分析，已经建立了牛、大鼠、海鸦和梭鱼胰岛素原前肽区域的部分氨基酸序列4,5,7。克隆的大鼠胰岛素I基因cDNA的核苷酸序列证实了大鼠胰岛素I原的氨基酸序列，并预测了前肽9 - 11的序列。像其他分泌蛋白的前肽一样，这种前肽有一个显著的疏水区。我们在此报道了从人胰岛素mRNA中制备的cDNA的克隆，并分析了克隆分子的核苷酸序列，包括编码前肽的区域以及分子的5 ‘和3 ’非翻译区域的部分。我们还比较了人类分子的结构与先前报道的大鼠mRNA9-11。
Insulin consists of two polypeptide chains, A (21 amino acids) and B (30 amino acids), linked by disulphide bonds. Both chains are derived from one precursor, proinsulin, which includes a connecting peptide (C) between the A and B chains, and which is excised before the secretion of insulin from the pancreatic B cells1. The observation that the C-peptide varies between species, in contrast to the highly conserved A and B sequences1–3, is consistent with the theory that it serves a purely structural function in insulin synthesis. Duringin vitrotranslation of insulin mRNA, a larger peptide containing about 25 additional residues at the N-terminal end (preproinsulin) is the primary product4–7. The prepeptide is cleaved to leave proinsulin during transport into the endoplasmic reticulum and is thought to direct this process specifically8. Using automated amino acid sequence analysis, the partial amino acid sequences of the prepeptide regions of bovine, rat, sea raven and anglerfish preproinsulin have been established4,5,7. The nucleotide sequences of the cloned cDNA and gene coding for rat insulin I have confirmed the amino acid sequence of rat proinsulin I, and have also predicted the sequence of the prepeptide9–11. Like the prepeptides of other secreted proteins, this prepeptide has a prominent hydrophobic region12. We report here the cloning of a cDNA prepared from human insulin mRNA and an analysis of the nucleotide sequence of the cloned molecule including the region coding for the prepeptide and portions of the 5′- and the 3′-untranslated regions of the molecule. We also compare the structure of the human molecule with the previously reported rat mRNA9–11.