The ligand-binding domain of rhodopsin and other G protein-linked receptors

Rhodopsin is a member of the very large family of G protein-linked receptors. The members of this family show clear signs of evolutionary relatedness, primarily in amino acid sequence homology, topographical structure of the proteins in the membrane, and the fact that all of the receptors function through the intermediary action of a GTP-binding regulatory protein or G protein. Recently, it has become clear that the structural similarity of these receptors extends well beyond the rather crude comparison of membrane topography. Reviewed here are several studies in which site-directed mutagenesis and active-site-directed reagents were used to show that the ligand-binding pockets of these receptors are highly similar. They are similar despite the fact that the structures of their various ligands are very different.