Identification of intramolecular interactions in adrenergic receptors

Adrenergic receptors are representative of a large family of plasma membrane receptors that interact with G proteins during the process of transmembrane signal transduction. G protein-coupled receptors have a primary structure that is homologous to bacteriorhodopsin and are proposed to have a similar three-dimensional structure; however, it has not yet been possible to examine this hypothesis experimentally. We have used a novel mutagenesis approach to identify intramolecular interactions. Our results indicate that specific amino acids in the seventh hydrophobic segment of alpha 2 and beta 2 adrenergic receptors lie adjacent to the first hydrophobic segment. These studies provide the first experimental evidence defining spatial relationships that exist in the three-dimensional structure of adrenergic receptors.