Vibrational spectroscopy analysis of ligand efficacy in human M 2 muscarinic acetylcholine receptor (M 2 R).

Autor: Katayama K; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Nagoya, 466-8555, Japan. Katayama.kota@nitech.ac.jp.; OptoBioTechnology Research Center, Nagoya Institute of Technology, Showa-ku, Nagoya, 466-8555, Japan. Katayama.kota@nitech.ac.jp.; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan. Katayama.kota@nitech.ac.jp., Suzuki K; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Nagoya, 466-8555, Japan., Suno R; Department of Medical Chemistry, Kansai Medical University, Hirakata, 573-1010, Japan., Kise R; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan., Tsujimoto H; Department of Cell Biology and Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan., Iwata S; Department of Cell Biology and Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan., Inoue A; Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, 980-8578, Japan., Kobayashi T; Department of Medical Chemistry, Kansai Medical University, Hirakata, 573-1010, Japan.; Japan Agency for Medical Research and Development, Core Research for Evolutional Science and Technology (AMED-CREST), Chiyoda-ku, Tokyo, 100-0004, Japan., Kandori H; Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Showa-ku, Nagoya, 466-8555, Japan. kandori@nitech.ac.jp.; OptoBioTechnology Research Center, Nagoya Institute of Technology, Showa-ku, Nagoya, 466-8555, Japan. kandori@nitech.ac.jp.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Nov 23; Vol. 4 (1), pp. 1321. Date of Electronic Publication: 2021 Nov 23.
DOI: 10.1038/s42003-021-02836-1
Abstrakt: The intrinsic efficacy of ligand binding to G protein-coupled receptors (GPCRs) reflects the ability of the ligand to differentially activate its receptor to cause a physiological effect. Here we use attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy to examine the ligand-dependent conformational changes in the human M 2 muscarinic acetylcholine receptor (M 2 R). We show that different ligands affect conformational alteration appearing at the C=O stretch of amide-I band in M 2 R. Notably, ATR-FTIR signals strongly correlated with G-protein activation levels in cells. Together, we propose that amide-I band serves as an infrared probe to distinguish the ligand efficacy in M 2 R and paves the path to rationally design ligands with varied efficacy towards the target GPCR.
(© 2021. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje