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Ligand Binding-Induced Structural Changes in the M2 Muscarinic Acetylcholine Receptor Revealed by Vibrational
Kota Katayama1,2, Kohei Suzuki1, Ryoji Suno3
1Department of Life Science and Applied Chemistry , Nagoya Institute of Technology , Showa-ku, Nagoya 466-8555 , Japan.
Abstract:
M2 muscarinic acetylcholine receptor (M2R) is a prototypical G protein-coupled receptor (GPCR) that responds to acetylcholine and mediates various cellular responses in the nervous system. Here, we used attenuated total reflection-Fourier transform infrared spectroscopy analyses on M2R reconstituted in a lipid membrane to understand the molecular mechanism behind the ligand binding-induced conformational changes. Upon agonist binding, M2R shows large spectral change of the amide-I band corresponding to backbone C═O stretch, which likely connects with the receptor activation in the lipid environment. These results pave the way to probe effects of different ligand binding on GPCRs using vibrational spectroscopy.
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