Mechanisms for activation and antagonism of an AMPA-sensitive glutamate receptor: crystal structures of the GluR2 ligand binding core.
By N. Armstrong, Eric Gouaux. Neuron, 2000
869 citations recorded by the source corpus.
Crystal structures of the GluR2 ligand binding core (S1S2) have been determined in the apo state and in the presence of the antagonist DNQX, the partial agonist kainate, and the full agonists AMPA and glutamate. The domains of the S1S2 ligand binding core are expanded in the apo state and contract upon ligand binding with the extent of domain separation decreasing in the order of apo > DNQX > kainate > glutamate approximately equal to AMPA. These results suggest that agonist-induced domain closure gates the transmembrane channel and the extent of receptor activation depends upon the degree of domain closure. AMPA and glutamate also promote a 180 degrees flip of a trans peptide bond in the ligand binding site. The crystal packing of the ligand binding cores suggests modes for subunit-subunit contact in the intact receptor and mechanisms by which allosteric effectors modulate receptor activity.
Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Spectroscopy
View Paper: https://www.semanticscholar.org/paper/3ed6a23eb13af814b443612f79d505ccbcb431e6
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Citations in the corpus
- Handbook of ion channels (2015, background): “The gamma carboxylate is stabilized against domain 2 via waters and backbone oxygens (Armstrong and Gouaux, 2000).”
- Glutamate Receptor Ion Channels: Structure, Regulation, and Function (2010, background): “CNQX and DNQX induce partial domain closure, consistent with the activity of a partial agonist (Armstrong and Gouaux, 2000).”
- Ionotropic and metabotropic glutamate receptor structure and pharmacology (2005, neutral): “Thus, although considered a bioisoster of the distal carboxy group of glutamate, the isoxazolol moiety of AMPA actually binds in a different manner to that of the carboxy group of glutamate (Armstrong and Gouaux 2000).”
- Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. (2009, neutral): “The ligand-binding domains are considerably more variable, although alignment of small regions of the S1 and S2 lobes of IRs and iGluRs allowed examination of conservation in amino acid positions that make direct contact with glutamate or artificial agonists in iGluRs (Armstrong et al., 1998; Armstr”