1p1q
From Proteopedia
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'''Crystal structure of the GluR2 ligand binding core (S1S2J) L650T mutant in complex with AMPA''' | '''Crystal structure of the GluR2 ligand binding core (S1S2J) L650T mutant in complex with AMPA''' | ||
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[[Category: Gouaux, E.]] | [[Category: Gouaux, E.]] | ||
[[Category: Mayer, M L.]] | [[Category: Mayer, M L.]] | ||
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| - | [[Category: | + | [[Category: Ionotropic glutamate receptor]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:34:19 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 01:34, 3 May 2008
Crystal structure of the GluR2 ligand binding core (S1S2J) L650T mutant in complex with AMPA
Overview
The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole) propionic acid (AMPA) receptor discriminates between agonists in terms of binding and channel gating; AMPA is a high-affinity full agonist, whereas kainate is a low-affinity partial agonist. Although there is extensive literature on the functional characterization of partial agonist activity in ion channels, structure-based mechanisms are scarce. Here we investigate the role of Leu-650, a binding cleft residue conserved among AMPA receptors, in maintaining agonist specificity and regulating agonist binding and channel gating by using physiological, x-ray crystallographic, and biochemical techniques. Changing Leu-650 to Thr yields a receptor that responds more potently and efficaciously to kainate and less potently and efficaciously to AMPA relative to the WT receptor. Crystal structures of the Leu-650 to Thr mutant reveal an increase in domain closure in the kainate-bound state and a partially closed and a fully closed conformation in the AMPA-bound form. Our results indicate that agonists can induce a range of conformations in the GluR2 ligand-binding core and that domain closure is directly correlated to channel activation. The partially closed, AMPA-bound conformation of the L650T mutant likely captures the structure of an agonist-bound, inactive state of the receptor. Together with previously solved structures, we have determined a mechanism of agonist binding and subsequent conformational rearrangements.
About this Structure
1P1Q is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes., Armstrong N, Mayer M, Gouaux E, Proc Natl Acad Sci U S A. 2003 May 13;100(10):5736-41. Epub 2003 May 2. PMID:12730367 Page seeded by OCA on Sat May 3 04:34:19 2008
