Allosteric Modulation of G Protein Coupled Receptors by Cytoplasmic, Transmembrane and Extracellular Ligands

Pharmaceuticals

Naveena Yanamala¹ 

[1] id="af1-pharmaceuticals-03-03324">Department of Structural Biology, School of Medicine, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15260, U

关键词: rhodopsin;    metabotropic glutamate receptors;    allosteric network;    communication;    membrane proteins;   

DOI  :  10.3390/ph3103324

来源: mdpi

【 摘 要 】

G protein coupled receptors (GPCRs) bind diverse classes of ligands, and depending on the receptor, these may bind in their transmembrane or the extracellular domains, demonstrating the principal ability of GPCRs to bind ligand in either domains. Most recently, it was also observed that small molecule ligands can bind in the cytoplasmic domain, and modulate binding and response to extracellular or transmembrane ligands. Thus, all three domains in GPCRs are potential sites for allosteric ligands, and whether a ligand is allosteric or orthosteric depends on the receptor. Here, we will review the evidence supporting the presence of putative binding pockets in all three domains of GPCRs and discuss possible pathways of communication between these pockets.

【 授权许可】

CC BY   
© 2010 by the authors; licensee MDPI, Basel, Switzerland.