Primary structure and tissue distribution of the orphanin FQ precursor.
Primary structure and tissue distribution of the orphanin FQ precursor.
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孤啡肽 FQ 前体的一级结构和组织分布。
DOI：
10.1073/pnas.93.16.8677
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发表时间：
1996
影响因子：
11.1
通讯作者：
Civelli,O
中科院分区：
文献类型：
--
作者：
Nothacker,HP;Reinscheid,RK;Mansour,A;Henningsen,RA;Ardati,A;MonsmaJr,FJ;Watson,SJ;Civelli,O
十七肽孤啡肽 FQ (OFQ) 是最近发现的一种神经肽，其结构特征让人想起阿片肽，并且是与阿片受体顺序相关的 G 蛋白偶联受体的内源配体。我们克隆了编码 OFQ 前体蛋白的人和大鼠 cDNA，以研究阿片类药物和 OFQ 系统之间存在的序列关系是否也在多肽前体水平上发现，特别是 OFQ 前体是否会像阿片类药物前体一样编码多种生物活性肽，并研究 OFQ 合成位点的区域分布。整个前体蛋白与阿片肽前体，特别是前强啡肽原和前脑啡肽原，表现出结构同源性。 OFQ 前体的预测氨基酸序列包含推定的信号肽和侧翼为一对碱性氨基酸残基的 OFQ 序列的一个副本。人类和大鼠前体的 OFQ 序列的羧基末端含有一段 28 个氨基酸，100% 保守，因此可能编码新型生物活性肽。合成了源自该片段的两种肽，但发现它们无法激活 OFQ 受体，这表明如果它们在体内产生，这些肽可能会识别与 OFQ 受体不同的受体。为了开始分析 OFQ mRNA 合成位点，对人和大鼠组织进行了 Northern 分析，结果表明 OFQ 前体 mRNA 主要在大脑中表达。大鼠脑切片的原位杂交证明了 OFQ 前体 mRNA 的区域分布模式，这与阿片肽前体的分布模式不同。这些数据证实，OFQ 系统在分子水平上不同于阿片类药物系统，尽管 OFQ 和阿片类药物前体可能源自共同的祖先基因。
The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligand to a G protein-coupled receptor sequentially related to the opioid receptors. We have cloned both the human and rat cDNAs encoding the OFQ precursor proteins, to investigate whether the sequence relationships existing between the opioid and OFQ systems are also found at the polypeptide precursor level, in particular whether the OFQ precursor would encode several bioactive peptides as do the opioid precursors, and to study the regional distribution of OFQ sites of synthesis. The entire precursor protein displays structural homology to the opioid peptide precursors, especially preprodynorphin and preproenkephalin. The predicted amino acid sequence of the OFQ precursor contains a putative signal peptide and one copy of the OFQ sequence flanked by pairs of basic amino acid residues. Carboxyl-terminal to the OFQ sequence, the human and rat precursors contain a stretch of 28 amino acids that is 100% conserved and thus may encode novel bioactive peptides. Two peptides derived from this stretch were synthesized but were found to be unable to activate the OFQ receptor, suggesting that if they are produced in vivo, these peptides would likely recognize receptors different from the OFQ receptor. To begin analyzing the sites of OFQ mRNA synthesis, Northern analysis of human and rat tissues were carried out and showed that the OFQ precursor mRNA is mainly expressed in the brain. In situ hybridization of rat brain slices demonstrated a regional distribution pattern of the OFQ precursor mRNA, which is distinct from that of the opioid peptide precursors. These data confirm that the OFQ system differs from the opioid system at the molecular level, although the OFQ and opioid precursors may have arisen from a common ancestral gene.