Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA:: Implications for receptor subunit selectivity

Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tertbutyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn2+ ions. (S)-ATPA induces a domain closure of ca. 21degrees compared to the apo form. The tertbutyl moiety of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors.