title: Anions mediate ligand binding in Adineta vaga glutamate receptor ion channels.
abstract: AvGluR1, a glutamate receptor ion channel from the primitive eukaryote Adineta vaga, is activated by alanine, cysteine, methionine, and phenylalanine, which produce lectin-sensitive desensitizing responses like those to glutamate, aspartate, and serine. AvGluR1 LBD crystal structures reveal an unusual scheme for binding dissimilar ligands that may be utilized by distantly related odorant/chemosensory receptors. Arginine residues in domain 2 coordinate the γ-carboxyl group of glutamate, whereas in the alanine, methionine, and serine complexes a chloride ion acts as a surrogate ligand, replacing the γ-carboxyl group. Removal of Cl(-) lowers affinity for these ligands but not for glutamate or aspartate nor for phenylalanine, which occludes the anion binding site and binds with low affinity. AvGluR1 LBD crystal structures and sedimentation analysis also provide insights into the evolutionary link between prokaryotic and eukaryotic iGluRs and reveal features unique to both classes, emphasizing the need for additional structure-based studies on iGluR-ligand interactions.
authors: Laboratory of Cellular and Molecular Neurophysiology, Porter Neuroscience Research Center, National Institute of Child Health and Human Development/NIH/DHHS, Bethesda, MD 20892, USA.
authors: Suvendu
authors: S
authors: Lomash
authors: Sagar
authors: S
authors: Chittori
authors: Patrick
authors: P
authors: Brown
authors: Mark L
authors: ML
authors: Mayer
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002712:Chlorides / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D015801:Helminth Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D007473:Ion Channels / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D007700:Kinetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000145:classification / Q000235:genetics; D012403:Rotifera / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D000596:Amino Acids; D002712:Chlorides; D015801:Helminth Proteins; D007473:Ion Channels; D008024:Ligands; D017470:Receptors, Glutamate; D011994:Recombinant Proteins