Ionotropic glutamate receptors (iGluRs) mediate excitatory synaptic tr
ansmission in vertebrates and invertebrates through ligand-induced ope
ning of transmembrane ion channels. iGluRs are segregated into three s
ubtypes according to their sensitivity to the agonists AMPA (alpha-ami
no-3-hydroxy-5-methyl-4-isoxazole propionic acid), kainate (a structur
al analogue of glutamate) or NMDA (N-methyl-D-aspartate) (Fig.1). iGlu
Rs are important in the development and function of the nervous system
, are essential in memory and learning, and are either implicated in o
r have causal roles in dysfunctions ranging from Alzheimer's, Parkinso
n's and Huntington's diseases, schizophrenia, epilepsy and Rasmussen's
encephalitis to stroke(1,2). Development of iGluR agonists and antago
nists has been hampered by a lack of high-resolution structural inform
ation. Here we describe the crystal structure of an iGluR ligand-bindi
ng region in a complex with the neurotoxin (agonist) kainate. The bilo
bed structure shows the determinants of receptor-agonist interactions
and how ligand-binding specificity and affinity are altered by remote
residues and the redox state of the conserved disulphide bond, The str
ucture indicates mechanisms for allosteric effector action and for lig
and-induced channel gating. The information provided by this structure
will be essential in designing new ligands.