Lindner Diana, Stichel Jan, Beck-Sickinger Annette G
Institute of Biochemistry, Faculty of Biosciences, Pharmacy, and Psychology, Leipzig University, Leipzig, Germany.
Nutrition. 2008 Sep;24(9):907-17. doi: 10.1016/j.nut.2008.06.025.
Many G-protein-coupled receptors belong to families of different receptor subtypes, which are recognized by a variety of distinct ligands. We summarize the current state of the art of the multireceptor/multiligand system of the so-called Y-receptor family. This family consists of four G-protein-coupled Y receptors in humans (hY(1), hY(2), hY(4), and hY(5)) and is activated by the so-called neuropeptide Y hormone family, which consists of three native peptide ligands named neuropeptide Y, pancreatic polypeptide, and peptide YY. We recently reported that one conserved aspartate residue in the third extracellular loop is essential for ligand binding in all four Y receptors, but binds the endogenous ligands in a different mode by interacting with different ligand arginine residues. By combining peptide synthesis to obtain chemically modified neuropeptide Y, peptide YY, and pancreatic polypeptide analogs, receptor mutagenesis, and receptor chimeras, we could trace binding and signaling to a molecular level. The data on the variation of the ligands and an overview of the currently known mutagenesis data are summarized and specific models for the binding mode of the three ligands in all four receptors are provided.
许多G蛋白偶联受体属于不同受体亚型的家族，它们可被多种不同的配体识别。我们总结了所谓Y受体家族的多受体/多配体系统的当前技术水平。该家族在人类中有四种G蛋白偶联的Y受体（hY(1)、hY(2)、hY(4)和hY(5)），并被所谓的神经肽Y激素家族激活，该家族由三种天然肽配体组成，分别名为神经肽Y、胰多肽和肽YY。我们最近报道，第三个细胞外环中的一个保守天冬氨酸残基对于所有四种Y受体的配体结合至关重要，但通过与不同的配体精氨酸残基相互作用，以不同的模式结合内源性配体。通过结合肽合成以获得化学修饰的神经肽Y、肽YY和胰多肽类似物、受体诱变和受体嵌合体，我们可以将结合和信号传导追溯到分子水平。总结了配体变异的数据以及当前已知的诱变数据概述，并提供了所有四种受体中三种配体结合模式的具体模型。
