Three-Dimensional Models of non-NMDA Glutamate Receptors
Michael J. Sutcliffe*, Z. Galen Wo¤, and Robert E. Oswald¤
*Department of Chemistry
University of Leicester
Leicester, LE1 7RH, UK
¤Department of Pharmacology
College of Veterinary Medicine
Cornell University
Ithaca, NY 14853 USA

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Abstract
Structural models have been produced for three types of non-NMDA ionotropic glutamate receptors: an AMPA receptor, GluR1; a kainate receptor, GluR6; and a low molecular weight kainate receptor from goldfish, GFKARa. 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 agonist binding. As a first approximation, the ion channel domain was modeled with a structure comprising a central antiparallel beta-barrel which partially crosses the membrane, and against which two 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.

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Title Page
Introduction
Methods
Results and Discussion: Sequence Alignment and Stoichiometry
Results and Discussion: Agonist Binding Domain
Results and Discussion: Membrane Domains
Summary
References
Acknowledgements