Molecular recognition of the NPY hormone family by their receptors
Molecular recognition of the NPY hormone family by their receptors
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DOI：
10.1016/j.nut.2008.06.025
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发表时间：
2008-09-01
期刊：
影响因子：
4.4
通讯作者：
Beck-Sickinger, Annette G.
中科院分区：
文献类型：
--
作者：
Lindner, Diana;Stichel, Jan;Beck-Sickinger, Annette G.
许多G蛋白偶联受体属于不同受体亚型的家族，其被多种不同的配体识别。我们总结了。所谓的Y-受体家族的多受体/多配体系统的现有技术。该家族由人体中的四种G蛋白偶联Y受体（hY（1）、hY（2）、hY（4）和hY（5））组成，并由所谓的神经肽Y激素家族激活，该家族由三种天然肽组成命名为神经肽Y、胰多肽和肽YY的肽配体。我们最近报道，一个保守的天冬氨酸残基在第三个细胞外环是必不可少的配体结合在所有四个Y受体，但结合内源性配体在不同的模式，通过与不同的配体精氨酸残基相互作用。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，我们可以在分子水平上追踪结合和信号传导。的配体的变化和概述目前已知的诱变数据的数据进行了总结，并提供了在所有四个受体的三个配体的结合模式的具体模型。(C)2008年爱思唯尔公司All rights reserved.
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. (C) 2008 Elsevier Inc. All rights reserved.