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Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors.
Tang, Tingting; Tan, Qiuxiang; Han, Shuo; Diemar, Anne; Löbner, Kristin; Wang, Hongyu; Schüß, Corinna; Behr, Victoria; Mörl, Karin; Wang, Mu; Chu, Xiaojing; Yi, Cuiying; Keller, Max; Kofoed, Jacob; Reedtz-Runge, Steffen; Kaiser, Anette; Beck-Sickinger, Annette G; Zhao, Qiang; Wu, Beili.
Afiliación
  • Tang T; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, UCAS, Hangzhou, China.
  • Tan Q; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Han S; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Diemar A; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Löbner K; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
  • Wang H; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
  • Schüß C; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Behr V; University of Chinese Academy of Sciences, Beijing, China.
  • Mörl K; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
  • Wang M; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
  • Chu X; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
  • Yi C; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Keller M; School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
  • Kofoed J; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Reedtz-Runge S; CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • Kaiser A; Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Regensburg, Germany.
  • Beck-Sickinger AG; Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark.
  • Zhao Q; Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark.
  • Wu B; Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Leipzig, Germany.
Sci Adv ; 8(18): eabm1232, 2022 May 06.
Article en En | MEDLINE | ID: mdl-35507650
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 Y1, Y2, and Y4 receptors in complex with NPY or PP, and the Gi1 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 Y1 receptor, but not with the Y2 and Y4 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Sci Adv Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos