title: Evolution of glutamate interactions during binding to a glutamate receptor.
abstract: Glutamate receptors are the predominant mediators of excitatory synaptic signals in the central nervous system and are important in learning and memory as well as in diverse neuropathologies including epilepsy and ischemia. Their primary function is to receive the chemical signal glutamate (1), which binds to an extracellular domain in the receptor, and convert it into an electrical signal through the formation of cation-permeable transmembrane channels. Recently described end-state apo and ligated structures of the ligand-binding domain of a rat glutamate receptor provide a first view of specific molecular interactions between the ligand and the receptor that are central to the allosteric regulation of function in this protein. Yet there is little information on the mechanism and the structures of intermediates (if any) formed during the ligand-binding process. Here we have used time-resolved vibrational spectroscopy to show that the process involves a sequence of interleaved ligand and protein changes that starts with the docking of glutamate at the alpha-carboxylate moiety and ends with the establishment of the interactions between the gamma-carboxylate of glutamate and the protein.
authors.affiliation: Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas 77030, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.forename: Mei
authors.initials: M
authors.lastname: Du
authors.forename: Gomathi
authors.initials: G
authors.lastname: Ramanoudjame
authors.forename: Vasanthi
authors.initials: V
authors.lastname: Jayaraman
mesh_terms: D018698:Glutamic Acid / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D014732:Vibration
chemical_list: D008024:Ligands; D017470:Receptors, Glutamate; D018698:Glutamic Acid