Tang, Tingting and Tan, Qiuxiang and Han, Shuo and Diemar, Anne and Lobner, Kristin and Wang, Hongyu and Schuess, Corinna and Behr, Victoria and Moerl, Karin and Wang, Mu and Chu, Xiaojing and Yi, Cuiying and Keller, Max and Kofoed, Jacob and Reedtz-Runge, Steffen and Kaiser, Anette and Beck-Sickinger, Annette G. and Zhao, Qiang and Wu, Beili (2022) Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors. SCIENCE ADVANCES, 8 (18): eabm1232. ISSN 2375-2548,
Full text not available from this repository. (Request a copy)Abstract
In response to three highly conserved neuropeptides, neuropeptide Y (NPY), peptide YY, and pancreatic polypeptide (PP), four G protein-coupled receptors mediate multiple essential physiological processes, such as food intake, vasoconstriction, sedation, and memory retention. Here, we report the structures of the human Y-1, Y-2, and Y-4 receptors in complex with NPY or PP, and the G(i)(1) protein. These structures reveal distinct binding poses of the peptide upon coupling to different receptors, reflecting the importance of the conformational plasticity of the peptide in recognizing the NPY receptors. The N terminus of the peptide forms extensive interactions with the Y-1 receptor, but not with the Y-2 and Y-4 receptors. Supported by mutagenesis and functional studies, subtype-specific interactions between the receptors and peptides were further observed. These findings provide insight into key factors that govern NPY signal recognition and transduction, and would enable development of selective drugs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NEUROPEPTIDE-Y; PANCREATIC-POLYPEPTIDE; FOOD-INTAKE; BINDING; Y-1; RESIDUES; DYNAMICS; LIGANDS; AGONIST; ANALOGS; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Jan 2024 14:01 |
| Last Modified: | 31 Jan 2024 14:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58572 |
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