Molecular recognition of the NPY hormone family by their receptors

Nutrition
Diana LindnerA G Beck-Sickinger

Abstract

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.

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Citations

Oct 21, 2010·The Journal of Biological Chemistry·Cornelia WaltherAnnette G Beck-Sickinger
Oct 18, 2012·American Journal of Physiology. Endocrinology and Metabolism·Jennifer M RojasKevin D Niswender
Nov 14, 2013·Seminars in Liver Disease·Jamie Eugene Mells, Frank A Anania
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Feb 26, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Cornelia WaltherAnnette G Beck-Sickinger
Oct 24, 2014·ChemMedChem·Verena M AhrensAnnette G Beck-Sickinger
Aug 14, 2010·Acta Biochimica Et Biophysica Sinica·Xuechen WuCheng-Wu Chi
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Sep 21, 2019·Biological Chemistry·Lisa Maria KöglerAnnette G Beck-Sickinger
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Sep 16, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jeannette M LaugwitzPeter Schmidt
Dec 22, 2017·ACS Chemical Biology·Jonathan LotzeAnnette G Beck-Sickinger
Feb 11, 2020·Journal of Proteome Research·Laura A FleitesMichelle L Heck
Nov 26, 2021·Angewandte Chemie·Sarina RudolfIrene Coin

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