The evolutionarily triumphant G-protein-coupled receptor
The evolutionarily triumphant G-protein-coupled receptor
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DOI：
10.1124/mol.63.6.1202
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发表时间：
2003-06-01
影响因子：
3.6
通讯作者：
Perez, DM
中科院分区：
文献类型：
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作者：
Perez, DM
在人类基因组中所有已知的蛋白质中，G 蛋白偶联受体 (GPCR) 可能是用途最广泛的。他们知道如何通过复制一个祖先基因并将其转化为数千种不同的蛋白质来操纵控制多样性的进化力量，这些蛋白质可以传导光、气味、味道、核苷酸、脂质、肽和各种其他化合物。它们似乎都是通过相同的机制来做到这一点，但可以选择性地与特定的配体和效应器密切相互作用。他们是怎么做到的？在本期《分子药理学》中，Fredriksson 等人 (2003) 付出巨大努力，使用 342 个功能性非嗅觉人类 GPCR 序列，首次提供了单个哺乳动物基因组中 GPCR 祖先的总体路线图。他们的结果表明，有五个主要家族：谷氨酸、视紫红质、粘附、卷曲/味道2和分泌素，形成了GRAFS分类系统。从基因（旁系同源物）的染色体位置和“指纹”基序的发现来看，作者支持这样的理论：GRAFS 家族中的 GPCR 具有共同的祖先，并通过基因复制和外显子改组而进化。他们的数据还构建了一个独特的 GPCR 家族，称为粘附家族，并表明两个味觉受体组（TAS1 和 TAS2）在系统发育上没有联系。分析将 TAS1 受体分为谷氨酸受体家族，而 TAS2 受体则归入卷曲受体家族。GPCR 非常多样化，并且对我们的生理学非常重要，因此它们是最受欢迎的药物靶点。它们包括大约 1000 至 2000 名成员，占人类基因组的 1%。即使线虫没有它们也无法生存，甚至可能需要更多它们。超过 1000 个 GPCR 构成线虫基因组的 5%（Bargmann，1998）。随着植物细胞因子 GPCR（来自拟南芥的 GCR1）的克隆，GPCR 的祖先更加古老，可能早于植物和动物的分化（Plakidou-Dymock 等，1998）。尽管尚未表征，但也有证据表明原生动物中存在 GPCR（New 和 Wong，1998）；当然，存在
Among all of the known proteins in the human genome, the G-protein-coupled receptors (GPCRs) may be the most versatile. They know how to manipulate the evolutionary forces that govern diversity by copying one ancestral gene and turning it into thousands of different proteins that can transduce light, smells, taste, nucleotides, lipids, peptides, and various other chemical compounds. They all seemingly do this by the same mechanism but can selectively and intimately interact with specific ligands and effectors. How did they do this? In this issue of Molecular Pharmacology, the tremendous effort of Fredriksson et al.(2003) provides the first overall road map of GPCR ancestry in a single mammalian genome using 342 functional nonolfactory human GPCR sequences. Their results show that there are five main families: Glutamate, Rhodopsin, Adhesion, Frizzled/taste2, and Secretin, forming the GRAFS classification system. From the chromosomal positions of the genes (paralogons) and the finding of “fingerprint” motifs, the authors support the theory that GPCRs in the GRAFS family share a common ancestor and evolved through gene duplication and exon shuffling. Their data also formulated a distinct family of GPCRs called the adhesion family and showed that the two taste receptor groups (TAS1 and TAS2) are not phylogenetically linked. The analysis divided the TAS1 receptors into the glutamate receptor family, whereas the TAS2 receptors grouped with Frizzled.The GPCRs are so diverse and important to our physiology that they are the most pursued as drug targets. They include about 1000 to 2000 members and comprise 1% of the human genome. Even nematodes cannot live without them or may even require them more; more than a thousand GPCRs make up 5% of the nematode genome (Bargmann, 1998). With the cloning of a plant cytokine GPCR, GCR1 from Arabidopsis thaliana, the ancestry of GPCRs is even more ancient and may predate the divergence of plants and animals (Plakidou-Dymock et al., 1998). Although not yet characterized, there is also evidence to suggest that GPCRs exist in protozoa (New and Wong, 1998); certainly, the presence of