Lysine Scanning Mutagenesis Delineates Structural Model of the Nicotinic Receptor Ligand Binding Domain

摘要: Nicotinic acetylcholine receptors (AChR) and their relatives mediate rapid chemical transmission throughout the nervous system, yet atomic structures remain elusive. Here we use lysine scanning mutagenesis to determine orientation of residue side chains toward core hydrophobic or surface hydrophilic environments this information build a structural model ligand binding region AChR from adult human muscle. The resulting side-chain orientations allow assignment equivalence between subunits an protein solved by x-ray crystallography, providing foundation for homology modeling. provides picture ACh site predicts novel pairs residues that stabilize subunit interfaces. overall results suggest can provide basis modeling other members superfamily as well proteins with repeating delimiting core.