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Molecular mechanism of agonist recognition by the ligand‐binding core of the ionotropic glutamate receptor 4
Author(s) -
Kasper Christina,
Frydenvang Karla,
Naur Peter,
Gajhede Michael,
Pickering Darryl S.,
Kastrup Jette Sandholm
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.11.005
Subject(s) - ampa receptor , ionotropic effect , ionotropic glutamate receptor , chemistry , ligand (biochemistry) , glutamate receptor , stereochemistry , metabotropic glutamate receptor 1 , agonist , receptor , metabotropic glutamate receptor , biophysics , biochemistry , biology
The α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) class of ionotropic glutamate receptors comprises four different subunits: iGluR1/iGluR2 and iGluR3/iGluR4 forming two subgroups. Three‐dimensional structures have been reported only of the ligand‐binding core of iGluR2. Here, we present two X‐ray structures of a soluble construct of the R/G unedited flip splice variant of the ligand‐binding core of iGluR4 (iGluR4 i (R)‐S1S2) in complex with glutamate or AMPA. Subtle, but important differences are found in the ligand‐binding cavity between the two AMPA receptor subgroups at position 724 (Tyr in iGluR1/iGluR2 and Phe in iGluR3/iGluR4), which in iGluR4 may lead to displacement of a water molecule and hence points to the possibility to make subgroup specific ligands.