Biosynthetic Short Neuropeptides: A Rational Theory Based on Experimental Results for the Missing Pain‐Relief Opioid Endomorphin Precursor Gene

Biosynthetic Short Neuropeptides: A Rational Theory Based on Experimental Results for the Missing Pain‐Relief Opioid Endomorphin Precursor Gene
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生物合成短神经肽:基于缺失的止痛阿片内吗啡肽前体基因实验结果的合理理论

DOI:
10.1002/cbic.201900317
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发表时间:
2019
期刊:
影响因子:
3.2
通讯作者:
Koyanagi Kanako O.
Koyanagi Kanako O.
中科院分区:
生物学3区
文献类型:
--
作者:
Matsushima Ayami;Sese Jun;Koyanagi Kanako O.

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内吗啡肽是与μ阿片受体强烈结合的神经肽,被认为在疼痛调节和其他生物学功能中发挥重要作用。目前已鉴定出两种内吗啡肽,分别是内吗啡肽-1和-2;两者都是四肽,仅在第三个位置上有一个氨基酸的差异。这两种肽都是从牛脑中分离出来的;然而,它们的前体基因尚未被鉴定。在本研究中,在表达序列标签数据库中发现了与内吗啡肽-1肽对应的核苷酸序列,并克隆了来自人脑互补DNA(cDNA)的前内吗啡肽样前体肽。cDNA由两个已经注释的预测基因的核苷酸序列组成,并且推定的肽与分离的内吗啡肽相差一个氨基酸。本文提出,基于已知蛋白质序列的相似性的自动化基因预测程序有可能遗漏未知的短蛋白质或肽前体。描述了如何从类似肽生产内吗啡肽的新概念。氧化修饰的碱基可能为理解基因组上的核苷酸序列与cDNA上的核苷酸序列之间的差异提供线索。
Endomorphins are neuropeptides that bind strongly to μ‐opioid receptors and are considered to play important roles in pain modulation and other biological functions. Two endomorphins have been identified, to date, endomorphine‐1 and ‐2; both are tetrapeptides and differ by only a single amino acid in the third position. Both peptides were isolated from bovine brains; however, their precursor genes have not been identified. In this study, a nucleotide sequence corresponding to the endomorphin‐1 peptide in an expressed sequence tag database has been found and a preproendomorphin‐like precursor peptide from human brain complementary DNA (cDNA) has been cloned. The cDNA consists of nucleotide sequences of two already annotated predicted genes, and the putative peptide differs by one amino acid from the isolated endomorphin peptides. It is proposed herein that there is the possibility of unknown short proteins or peptide precursors being missed by automated gene prediction programs based on similarities of known protein sequences. A novel concept of how to produce endomorphins from a similar peptide is described. The oxidatively modified base might provide a clue for understanding discrepancies between nucleotide sequences on the genome and those on cDNAs.
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