title: Structural insights into ligand recognition and selectivity for classes A, B, and C GPCRs.
abstract: The G protein-coupled receptor (GPCR) superfamily constitutes the largest collection of cell surface signaling proteins with approximately 800 members in the human genome. GPCRs regulate virtually all aspects of physiology and they are an important class of drug targets with ~30% of drugs on the market targeting a GPCR. Breakthroughs in GPCR structural biology in recent years have significantly expanded our understanding of GPCR structure and function and ushered in a new era of structure-based drug design for GPCRs. Crystal structures for nearly thirty distinct GPCRs are now available including receptors from each of the major classes, A, B, C, and F. These structures provide a foundation for understanding the molecular basis of GPCR pharmacology. Here, we review structural mechanisms of ligand recognition and selectivity of GPCRs with a focus on selected examples from classes A, B, and C, and we highlight major unresolved questions for future structural studies.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Booe
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: augen-pioszak@ouhsc.edu.
authors.forename: Augen A
authors.initials: AA
authors.lastname: Pioszak
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled
keywords: GPCR structure; GPCR subtype; Ligand recognition; Subtype selectivity; X-ray crystallography