title: Is the isolated ligand binding domain a good model of the domain in the native receptor?
abstract: Numerous studies have used the atomic level structure of the isolated ligand binding domain of the glutamate receptor to elucidate the agonist-induced activation and desensitization processes in this group of proteins. However, no study has demonstrated the structural equivalence of the isolated ligand binding fragments and the protein in the native receptor. In this report, using visible absorption spectroscopy we show that the electronic environment of the antagonist 6-cyano-7-nitro-2,3-dihydroxyquinoxaline is identical for the isolated protein and the native glutamate receptors expressed in cells. Our results hence establish that the local structure of the ligand binding site is the same in the two proteins and validate the detailed structure-function relationships that have been developed based on a comparison of the structure of the isolated ligand binding domain and electrophysiological consequences in the native receptor.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Dustin
authors.initials: D
authors.lastname: Deming
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Jayaraman
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000737:chemistry*; D001665:Binding Sites; D001669:Biochemical Phenomena; D001671:Biochemistry; D002460:Cell Line; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017470:Receptors, Glutamate / Q000378:metabolism; D013053:Spectrophotometry; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: D018076:DNA, Complementary; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D017470:Receptors, Glutamate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione