UNIT 1.21 Overview of Receptor Allosterism

  1. Karen J. Gregory,
  2. Patrick M. Sexton,
  3. Arthur Christopoulos

Published Online: 1 DEC 2010

DOI: 10.1002/0471141755.ph0121s51

Current Protocols in Pharmacology

Current Protocols in Pharmacology

How to Cite

Gregory, K. J., Sexton, P. M. and Christopoulos, A. 2010. Overview of Receptor Allosterism. Current Protocols in Pharmacology. 51:1.21:1.21.1–1.21.34.

Author Information

  1. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, Victoria, Australia

Publication History

  1. Published Online: 1 DEC 2010
  2. Published Print: DEC 2010


In addition to the orthosteric site, which recognizes endogenous ligands, most G protein–coupled receptors (GPCRs) possess topographically distinct allosteric sites that can be recognized by small molecules and accessory cellular proteins. Ligand binding to allosteric sites promotes a conformational change in the GPCR that can alter orthosteric ligand affinity and/or efficacy. Moreover, there has been an increase in recent years in the identification of allosteric agonists that can directly activate the receptor in the absence of orthosteric ligand. Allosteric sites are attractive therapeutic targets because they can be exploited to achieve modes of selectivity and signaling that are not attainable by orthosteric means. However, an important challenge in this field remains the quantification of the myriad of possible allosteric effects on binding and signaling events. This unit provides an overview on GPCR allosterism and the different pharmacological approaches to understanding allosteric behaviors. Curr. Protoc. Pharmacol. 51:1.21.1-1.21.34. © 2010 by John Wiley & Sons, Inc.


  • allosteric ternary complex model;
  • bitopic;
  • G protein–coupled receptor;
  • modulator;
  • orthosteric;
  • radioligand binding