Letter abstract
Nature Chemical Biology 1, 329 - 332 (2005)
Published online: 25 September 2005 | doi:10.1038/nchembio738
Evolution of glutamate interactions during binding to a glutamate receptor
Qing Cheng1, Mei Du1, Gomathi Ramanoudjame1 & Vasanthi Jayaraman1
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 ischemia1, 2, 3, 4, 5. 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 channels6, 7, 8, 9. 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 protein7, 10, 11, 12, 13, 14, 15. Yet there is little information on the mechanism and the structures of intermediates (if any) formed during the ligand-binding process16. 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 
-carboxylate moiety and ends with the establishment of the interactions between the 
-carboxylate of glutamate and the protein.
- 6431 Fannin, Department of Integrative Biology and Pharmacology, University of Texas Health Science Center, Houston, Texas 77030, USA.
Correspondence to: Vasanthi Jayaraman1 e-mail: vasanthi.jayaraman@uth.tmc.edu
