title: Heterologous GPCR expression: a bottleneck to obtaining crystal structures.
abstract: G protein-coupled receptors (GPCRs) are an important, medically relevant class of integral membrane proteins. Laboratories throughout all disciplines of science devote time and energy into developing practical methods for the discovery, isolation, and characterization of these proteins. Since the crystal structure of rhodopsin was solved 6 years ago, the race to determine high-resolution structures of more GPCRs has gained momentum. Since certain GPCRs are currently produced at sufficient levels for X-ray crystallography trials, it is speculated that heterologous expression of GPCRs may no longer be a bottleneck in obtaining crystal structures. This Review focuses on the current approaches in heterologous expression of GPCRs and explores the problems associated with obtaining crystal structures from GPCRs expressed in different systems. Although milligram amounts of certain GPCRs are attainable, the majority of GPCRs are still either produced at very low levels or not at all. Developing reliable expression techniques for GPCRs is still a major priority for the structural characterization of GPCRs.
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19711, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: McCusker
authors.forename: Steven E
authors.initials: SE
authors.lastname: Bane
authors.forename: Michelle A
authors.initials: MA
authors.lastname: O'Malley
authors.forename: Anne Skaja
authors.initials: AS
authors.lastname: Robinson
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015003:Yeasts / Q000235:genetics
chemical_list: D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins