The tethered agonist approach to mapping ion channel proteins – toward a structural model for the agonist binding site of the nicotinic acetylcholine receptor Original Research Article

Background: The integral membrane proteins of neurons and other excitable cells are generally resistant to high resolution structural tools. Structure–function studies, especially those enhanced by the nonsense suppression methodology for unnatural amino acid incorporation, constitute one of the most powerful probes of ion channels and related structures. The nonsense suppression methodology can also be used to incorporate functional side chains designed to deliver novel structural probes to membrane proteins. In this vein, we sought to generalize a potentially powerful tool – the tethered agonist approach – for mapping the agonist binding site of ligand-gated ion channels.