1p1w
From Proteopedia
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| - | [[Image:1p1w.jpg|left|200px]] | + | [[Image:1p1w.jpg|left|200px]] |
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| - | '''Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and in complex with AMPA''' | + | {{Structure |
| + | |PDB= 1p1w |SIZE=350|CAPTION= <scene name='initialview01'>1p1w</scene>, resolution 1.80Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=AMQ:(S)-ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID'>AMQ</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= GRIA2 OR GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and in complex with AMPA''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1P1W is a [ | + | 1P1W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P1W OCA]. |
==Reference== | ==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:[http:// | + | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12730367 12730367] |
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: ionotropic glutamate receptor]] | [[Category: ionotropic glutamate receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:18:46 2008'' |
Revision as of 11:18, 20 March 2008
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| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Gene: | GRIA2 OR GLUR2 (Rattus norvegicus) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and 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
1P1W 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
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