研究目的

To understand the molecular mechanism behind the ligand binding-induced conformational changes in the M2 muscarinic acetylcholine receptor (M2R) using Attenuated Total Reflection-Fourier Transform Infrared (ATR-FTIR) spectroscopy.

研究成果

The study reveals structural differences induced by agonist and antagonist binding to M2R, indicating an agonist-specific recognition and binding which is largely achieved by large conformational changes in the receptor. The results provide new insight into the unresolved issue of ligand-induced structural changes and stereoselectivity of M2R, highlighting that ATR-FTIR spectroscopy can greatly contribute to elucidate the underlying mechanism of GPCR activation through ligand binding at the molecular level.

研究不足

The study captures only specific conformations in a local energy minimum, and the dynamic structural changes associated with receptor activation in lipid environment remain partially unclear. Additionally, the technique requires isotopic labeling and/or site-directed mutations for some membrane protein systems.