1p1n
From Proteopedia
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|PDB= 1p1n |SIZE=350|CAPTION= <scene name='initialview01'>1p1n</scene>, resolution 1.6Å | |PDB= 1p1n |SIZE=350|CAPTION= <scene name='initialview01'>1p1n</scene>, resolution 1.6Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=KAI:3- | + | |LIGAND= <scene name='pdbligand=KAI:3-CARBOXYMETHYL-4-ISOPROPYL-PYRROLIDINE-2-CARBOXYLIC+ACID'>KAI</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=[[1p1o|1P1O]], [[1p1q|1P1Q]], [[1p1u|1P1U]], [[1p1w|1P1W]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p1n OCA], [http://www.ebi.ac.uk/pdbsum/1p1n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1p1n RCSB]</span> | ||
}} | }} | ||
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[[Category: Gouaux, E.]] | [[Category: Gouaux, E.]] | ||
[[Category: Mayer, M L.]] | [[Category: Mayer, M L.]] | ||
| - | [[Category: KAI]] | ||
[[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 22:53:31 2008'' |
Revision as of 19:53, 30 March 2008
| |||||||
| , resolution 1.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | GRIA2 OR GLUR2 (Rattus norvegicus) | ||||||
| Related: | 1P1O, 1P1Q, 1P1U, 1P1W
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
GluR2 Ligand Binding Core (S1S2J) Mutant L650T in Complex with Kainate
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
1P1N 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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