G-protein coupled receptors (GPCRs) mediate a large number of biological pathways and are major therapeutic
targets. One of the most exiting phenomena of GPCRs is their ability to interact with other GPCRs. GPCRGPCR
interactions, also known as GPCR oligomerization, may create various functional entities such as homo- and
heterodimers and also form complex multimeric GPCR clusters. In many biological systems, GPCR-GPCR interactions
are crucial for signal regulation. The interaction with other receptors results in allosteric modifications of GPCRs
through conformational changes. Allosteric inhibition of GPCRs is considered an attractive strategy for drug development
and does not involve targeting the orthosteric site. Understanding the nature of GPCR-GPCR interactions is mandatory
for developing allosteric inhibitors. Studying GPCR-GPCR interactions is a challenging task and many methods
have been developed to analyze these events. This review will highlight some of the methods developed to study
GPCR-GPCR interactions and will describe pivotal studies that provided the basic understanding of the importance of
GPCR oligomerization. We will also describe the significance of GPCR interaction networks for drug development.
Recent studies will be reviewed to illustrate the use of state-of-the-art biophysical and spectroscopic methods for the
discovery of GPCR oligomerization modulators.
Keywords: Allosteric inhibition, chemokine receptors, GPCR inhibition, GPCR-GPCR interactions, GPCR oligomerization, Gprotein
coupled receptors, Helix mimetic
Rights & PermissionsPrintExport