MODES OF PEPTIDE BINDING IN G-PROTEIN-COUPLED RECEPTORS

The G-protein coupled seven transmembrane domain receptors bind a wide variety of ligands of different molecular size ranging from small mon oamines to large neuropeptides and peptide hormones. This review summa rises data from studies on the localisation of the binding site for a few neuropeptides in their receptors and compares this to the binding pockets for non peptide ligands. The main conclusion is that neuropept ide binding involves residues on the top of several transmembrane doma ins and in extracellular loops of the receptors while the non peptide type ligands to the same receptors tend to bind deeper in the plane of the membrane, between several transmembrane domains-similarly to mono amines. Thus the antagonism exerted by most of the non peptide type li gands is an allosteric phenomenon whereby binding of these to another site than the peptide binding site stabilises a ''non agonist'' bindin g, and for signalling inactive, conformation of the 7 TM receptor.