Real-time tilting and twisting motions of ligand-bound states of α7 nicotinic acetylcholine receptor

• DOI: 10.1007/s00249-023-01693-6
• Publication Date: 2024-01-17T17:41:18Z
• Authors: Yue Yang; Tatsuya Arai; Daisuke Sasaki; Masahiro Kuramochi; Hidetoshi Inagaki; Sumiko Ohashi; Hiroshi Sekiguchi; Kazuhiro Mio; Tai Kubo; Yuji C. Sasaki
• Keywords: 0301 basic medicine; 0303 health sciences; Ivermectin; alpha7 Nicotinic Acetylcholine Receptor; Allosteric Regulation; Original Article; Receptors, Nicotinic; Ligands; Acetylcholine

Abstract The α7 nicotinic acetylcholine receptor is a member of the family and composed five subunits arranged symmetrically around central pore. It localized in nervous system immune cells could be target for treating Alzheimer’s disease schizophrenia. Acetylcholine ligand that opens channel, although prolonged application rapidly decreases response. Ivermectin was reported as one positive allosteric modulators, since binding to channel enhances acetylcholine-evoked currents. One research has suggested tilting motions are responsible opening activation. To verify this hypothesis applies receptor, we utilized diffracted X-ray tracking method monitor stable twisting motion nAChR without ligand, with acetylcholine, Ivermectin, both them. results show twists counterclockwise transiently opening, transitioning desensitized state presence clockwise Ivermectin. We propose conformational transition ACh-bound may due collective subunits, resulting compression movement, either downward or upward, more thus manifesting motions. These possibly represent from resting potentially state.