한빛사논문
Chaehee Park1,7, Jinuk Kim1,7, Seung-Bum Ko1, Yeol Kyo Choi2, Hyeongseop Jeong3, Hyeonuk Woo4, Hyunook Kang1, Injin Bang1,6, Sang Ah Kim1,5, Tae-Young Yoon1,5, Chaok Seok4, Wonpil Im2 & Hee-Jung Choi1,*
1Department of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea. 2Departments of Biological Sciences and Chemistry, Lehigh University, Bethlehem, PA 18015, USA. 3Center for Electron Microscopy Research, Korea Basic Science Institute, Chungcheongbuk-do 28119, Republic of Korea. 4Department of Chemistry, Seoul National University, Seoul 08826, Republic of Korea. 5Institute for Molecular Biology and Genetics, Seoul National University, Seoul 08826, Republic of Korea. 6Present address: Perlmutter Cancer Center, New York University Langone Health, and Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York 10016 NY, USA. 7These authors contributed equally: Chaehee Park, Jinuk Kim.
*Corresponding author.
Abstract
Neuropeptide Y (NPY) is highly abundant in the brain and involved in various physiological processes related to food intake and anxiety, as well as human diseases such as obesity and cancer. However, the molecular details of the interactions between NPY and its receptors are poorly understood. Here, we report a cryo-electron microscopy structure of the NPY-bound neuropeptide Y1 receptor (Y1R) in complex with Gi1 protein. The NPY C-terminal segment forming the extended conformation binds deep into the Y1R transmembrane core, where the amidated C-terminal residue Y36 of NPY is located at the base of the ligand-binding pocket. Furthermore, the helical region and two N-terminal residues of NPY interact with Y1R extracellular loops, contributing to the high affinity of NPY for Y1R. The structural analysis of NPY-bound Y1R and mutagenesis studies provide molecular insights into the activation mechanism of Y1R upon NPY binding.
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