title: Importance of the extracellular loops in G protein-coupled receptors for ligand recognition and receptor activation.
abstract: G protein-coupled receptors (GPCRs) are the major drug target of medicines on the market today. Therefore, much research is and has been devoted to the elucidation of the function and three-dimensional structure of this large family of membrane proteins, which includes multiple conserved transmembrane domains connected by intra- and extracellular loops. In the last few years, the less conserved extracellular loops have garnered increasing interest, particularly after the publication of several GPCR crystal structures that clearly show the extracellular loops to be involved in ligand binding. This review will summarize the recent progress made in the clarification of the ligand binding and activation mechanism of class-A GPCRs and the role of extracellular loops in this process.
authors.affiliation: Division of Medicinal Chemistry, Leiden/Amsterdam Centre for Drug Research, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: M C
authors.initials: MC
authors.lastname: Peeters
authors.forename: G J P
authors.initials: GJ
authors.lastname: van Westen
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: A P
authors.initials: AP
authors.lastname: IJzerman
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D012243:Rhodopsin