1p1w
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1p1w |SIZE=350|CAPTION= <scene name='initialview01'>1p1w</scene>, resolution 1.80Å | |PDB= 1p1w |SIZE=350|CAPTION= <scene name='initialview01'>1p1w</scene>, resolution 1.80Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=AMQ:(S)-ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC+ACID'>AMQ</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= GRIA2 OR GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | |GENE= GRIA2 OR GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1p1n|1P1N]], [[1p1o|1P1O]], [[1p1q|1P1Q]], [[1p1u|1P1U]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p1w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p1w OCA], [http://www.ebi.ac.uk/pdbsum/1p1w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p1w RCSB]</span> | ||
}} | }} | ||
| Line 25: | Line 28: | ||
[[Category: Gouaux, E.]] | [[Category: Gouaux, E.]] | ||
[[Category: Mayer, M L.]] | [[Category: Mayer, M L.]] | ||
| - | [[Category: AMQ]] | ||
| - | [[Category: SO4]] | ||
[[Category: ampa receptor]] | [[Category: ampa receptor]] | ||
[[Category: ion channel]] | [[Category: ion channel]] | ||
[[Category: ionotropic glutamate receptor]] | [[Category: ionotropic glutamate receptor]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:53:38 2008'' |
Revision as of 19:53, 30 March 2008
| |||||||
| , resolution 1.80Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | GRIA2 OR GLUR2 (Rattus norvegicus) | ||||||
| Related: | 1P1N, 1P1O, 1P1Q, 1P1U
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| 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
Page seeded by OCA on Sun Mar 30 22:53:38 2008
