Christopher K. Surratt and Wendy R. Adams Pages 315 - 324 ( 10 )
As a whole, the G protein-coupled receptor (GPCR) superfamily displays no overall sequence homology. Nevertheless, enough short sequences and even individual amino acid residues are shared by these receptors to afford a common three-dimensional structure and a similar signal transduction mechanism. Some of these sequence commonalities, or structural motifs, are dedicated to preserving receptor infrastructure, while others are critical to agonistmediated signaling. Certain structural motifs common to GPCRs and other signal transducing integral membrane proteins are present in the conventional opioid receptors, although several of the motifs are not well characterized in this receptor family. Here we focus on six structural motifs found in the mu, delta and kappa opioid receptors as well as the opioid like receptor ORL-1. The motifs are discussed in terms of their dynamic roles in the signaling mechanism documented for several Class A GPCRs including the opioid receptors. Clarification of the roles of GPCR structural motifs provides a blueprint for structure-function studies on newly discovered or recently cloned receptors in the superfamily. Characterization of these motifs in the opioid receptors should enhance understanding of what makes an opioid ligand a full, partial or inverse agonist or antagonist at a given receptor, possibly leading to rational design of therapeutics useful for combating opiate dependence or for pain management.
g proteins, opioid-like (orl-1), signal transduction
Division of Pharmaceutical Sciences, Mylan School of Pharmacy, Duquesne University, Pittsburgh,Pennsylvania, 15282, USA.