Three-dimensional models of non-NMDA glutamate receptors.
Structural models have been produced for three types of non-NMDA inotropic glutamate receptors: an AMPA receptor, GluR1, a kainate receptor, GluR6; and a low-molecular-weight kainate receptor from goldfish, GFKAR alpha. Modeling was restricted to the domains of the proteins that bind the neurotransmitter glutamate and that form the ion channel. Model building combined homology modeling, distance geometry, molecular mechanics, interactive modeling, and known constraints. The models indicate new potential interactions in the extracellular domain between protein and agonists, and suggest that the transition from the "closed" to the "open" state involves the movement of a conserved positive residue away from, and two conserved negative residues into, the extracellular entrance to the pore upon binding. As a first approximation, the ion channel domain was modeled with a structure comprising a central antiparallel beta-barrel that partially crosses the membrane, and against which alpha-helices from each subunit are packed; a third alpha-helix packs against these two helices in each subunit. Much, but not all, of the available data were consistent with this structure. Modifying the beta-barrel to a loop-like topology produced a model consistent with available data.
Sutcliffe
M J
MJ
Department of chemistry, University of Leicester, England.
Wo
Z G
ZG
Oswald
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055592:Biophysical Phenomena; D001703:Biophysics; D004220:Disulfides / Q000737:chemistry; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D006054:Goldfish; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D018091:Receptors, AMPA / Q000737:chemistry / Q000235:genetics; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D000097806:GluK2 Kainate Receptor
D004220:Disulfides; D018690:Excitatory Amino Acid Agonists; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D000097806:GluK2 Kainate Receptor