Plasmon resonance studies of agonist/antagonist binding to the human delta-opioid receptor: New structural insights into receptor-ligand interactions

Structural changes accompanying the binding of ligands to the cloned human delta -opioid receptor immobilized in a solid-supported lipid bilayer have been investigated using coupled plasmon-waveguide resonance spectroscopy. T his highly sensitive technique directly monitors mass density, conformation , and molecular orientation changes occurring in anisotropic thin films and allows direct determination of binding constants. Although both agonist bi nding and antagonist binding to the receptor cause increases in molecular o rdering within the proteolipid membrane, only agonist binding induces an in crease in thickness and molecular packing density of the membrane. This is a consequence of mass movements perpendicular to the plane of the bilayer o ccurring within the lipid and receptor components. These results are consis tent with models of receptor function that involve changes in the orientati on of transmembrane helices.