G protein-coupled receptor allosterism and complexing.

Allostery at G protein-coupled receptor homo- and heteromers: uncharted pharmacological landscapes.

For many years seven transmembrane domain G protein-coupled receptors (GPCRs) were thought to exist and function exclusively as monomeric units. However, evidence both from native cells and heterologous expression systems has demonstrated that GPCRs can both traffic and signal within higher-order complexes. As for other protein-protein interactions, conformational changes in one polypeptide, in...

Allosterism within G Protein-Coupled Receptor Oligomers: Back to Symmetry

Quantitative Measure of Receptor Agonist and Modulator Equi-Response and Equi-Occupancy Selectivity.

G protein-coupled receptors (GPCRs) are an important class of drug targets. Quantitative analysis by global curve fitting of properly designed dose-dependent GPCR agonism and allosterism data permits the determination of all affinity and efficacy parameters based on a general operational model. We report here a quantitative and panoramic measure of receptor agonist and modulator equi-response a...

G-protein Coupled Receptor Dimerization

A growing body of evidence suggests that GPCRs exist and function as dimers or higher oligomers. The evidence for GPCR dimerization comes from biochemical, biophysical and functional studies. In addition, researchers have shown the occurrence of heterodimerization between different members of the GPCR family. Two receptors can interact with each other to make a dimer through their extracellular...

Apelin: A promising therapeutic target? (Part 1)

Apelin is a recently discovered bioactive peptide, known to be an endogenous high-affinity ligandfor the previously orphan G protein-coupled receptor APJ. Apelin/APJ as a novel signaling pathwayhas been shown to play many crucial roles in cardiovascular function, blood pressure regulation, fluidhomeostasis, feeding behavior, obesity, type 2 diabetes mellitus, adipoinsular axis regulation, cellp...