PT  - JOURNAL ARTICLE
AU  - Banke, T. G.
AU  - Greenwood, J. R.
AU  - Christensen, J. K.
AU  - Liljefors, T.
AU  - Traynelis, S. F.
AU  - Schousboe, A.
AU  - Pickering, Darryl S.
TI  - Identification of Amino Acid Residues in GluR1 Responsible for Ligand Binding and Desensitization
AID  - 10.1523/JNEUROSCI.21-09-03052.2001
DP  - 2001 May 01
TA  - The Journal of Neuroscience
PG  - 3052--3062
VI  - 21
IP  - 9
4099  - http://www.jneurosci.org/content/21/9/3052.short
4100  - http://www.jneurosci.org/content/21/9/3052.full
SO  - J. Neurosci.2001 May 01; 21
AB  - Although GluR1o and GluR3o are homologous at the amino acid level, GluR3o desensitizes approximately threefold faster than GluR1o. By creating chimeras of GluR1o and GluR3o and point amino acid exchanges in their S2 regions, two residues were identified to be critical for GluR1o desensitization: Y716 and the R/G RNA-edited site, R757. With creation of the double-point mutant (Y716F, R757G)GluR1o, complete exchange of the desensitization rate of GluR1o to that of GluR3o was obtained. In addition, both the potency and affinity of the subtype-selective agonist bromohomoibotenic acid were exchanged by the Y716F mutation. A model is proposed of the AMPA receptor binding site whereby a hydrogen-bonding matrix of water molecules plays an important role in determining both ligand affinity and receptor desensitization properties. Residues Y716 in GluR1 and F728 in GluR3 differentially interact with this matrix to affect the binding affinity of some ligands, providing the possibility of developing subtype-selective compounds.