Nicotinic Receptor Binding Site Probed with Unnatural Amino Acid Incorporation inIntact Cells

摘要

In the study of membrane-bound receptor, channel, and transporter proteins,classical pharmacology has defined highly specific agonists and antagonists; and quantitative structure-activity studies have generated many hypotheses concerning ligand-receptor interactions. More recently, the combination of site-directed mutagenesis and heterologous expression has enabled functional studies on the consequences of structural modifications of the receptors. In the absence of atomic-scale structural data for membrane-bound receptors, these methods provide detailed information for studying ligand-receptor interactions. First generation mutagenesis methodologies employed the normal translation machinery such that a residue of interest could be changed to any of the other 19 natural amino acids.