Nicotinic receptors in wonderland

The structure of a soluble homopentameric homologue of the N-terminal extracellular domain of the nicotinic acetylcholine (ACh) receptor has recently been determined at the atomic level. These data reveal the three-dimensional structure of the binding site for ACh and nicotinic ligands. The ACh-binding sites are located at subunit boundaries in an equatorial position and are framed by residues previously identified in nicotinic receptors, by photoaffinity labelling and mutagenesis experiments, as being crucial for ligand binding. On this basis, a hypothetical mechanism for the allosteric transitions of the nicotinic receptors is suggested.