The state of GPCR research in 2004

  title={The state of GPCR research in 2004},
  author={Clare Udras Ellis},
  journal={Nature Reviews Drug Discovery},
  • C. Ellis
  • Published 1 July 2004
  • Biology
  • Nature Reviews Drug Discovery
G-protein-coupled receptors (GPCRs) comprise the largest single class of cell-surface receptors, and have a history of being excellent therapeutic targets for a number of diseases. Yet several fundamental questions remain regarding their underlying biology, and many GPCRs that could be promising targets for drug discovery are still uncharacterized at the level of identified ligand or biological function. In an attempt to find some answers, we posed 20 questions of fundamental importance to the… 
RAMPs as drug targets.
The receptor activity-modifying protein (RAMP) family of membrane proteins regulates G protein-coupled receptor (GPCR) function in several ways and may be exploited as drug targets, offering new opportunities for regulating the function of therapeutically relevant RAMP-interacting GPCRs.
GPCRs: Lipid-Dependent Membrane Receptors That Act as Drug Targets
The role of membrane cholesterol in GPCR function is discussed with specific example of the receptor and an emerging and important concept is oligomerization of GPCRs and its role in G PCR function and signaling.
The function of G-protein coupled receptors and membrane cholesterol: specific or general interaction?
The nature of cholesterol dependence of GPCR function is highlighted by taking a few known examples and suggesting alterations in the membrane physical properties induced by cholesterol.
Sphingolipids in the function of G protein-coupled receptors.
Receptors as Drug Targets
Concepts such as receptor constitutive activity, internalization and dimerization add additional complexity to the role of receptors in tissue function and in precisely characterizing their role in homeostasis and disease.
An improved classification of G-protein-coupled receptors using sequence-derived features
High accuracies are achieved when predicting GPCRs at all the five levels with the proposed PCA-GPCR method, believed to be capable of capturing information about amino acid composition, sequence order as well as various physicochemical properties of proteins.
G-protein-coupled receptor signalling through protein networks.
This short review provides a broad, and therefore necessarily incomplete and personal, overview of G-protein-coupled receptors, which are often targets for a wide range of important drugs: their structure, function and interactions with associated proteins.


G-Protein-coupled receptor oligomerization and its potential for drug discovery
This review provides a synopsis of the current thinking surrounding GPCR homo-oligomerization and hetero-OLigomersization and shows how new models point towards unexplored avenues in the development of new therapies.
Uncovering molecular mechanisms involved in activation of G protein-coupled receptors.
The goal of the present review is to specifically address the physical changes linking agonist binding to receptor activation and subsequent transduction of the signal to the associated G protein on the cytoplasmic side of the membrane and to other putative signaling pathways.
The identification of ligands at orphan G-protein coupled receptors.
The completion of the human genome sequencing project has identified approximately 720 genes that belong to the G-protein coupled receptor (GPCR) superfamily. Approximately half of these genes are
Efficacy at g-protein-coupled receptors
  • T. Kenakin
  • Biology
    Nature Reviews Drug Discovery
  • 2002
This review discusses the intimate relationship between the affinity of a ligand for its receptor, and the probability that the binding of the ligand will produce some change in the receptor, resulting in efficacy.
Chimaeric G alpha proteins: their potential use in drug discovery.
To better understand the domains involved in the interactions between G protein-coupled receptors, G proteins and effector polypeptides and the fine details of these contacts, a wide range of chimaeric G protein alpha subunits have been produced.