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| - | [[Image:1p1w.jpg|left|200px]] | + | {{Seed}} |
| | + | [[Image:1p1w.png|left|200px]] |
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| | {{STRUCTURE_1p1w| PDB=1p1w | SCENE= }} | | {{STRUCTURE_1p1w| PDB=1p1w | SCENE= }} |
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| - | '''Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and in complex with AMPA'''
| + | ===Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and in complex with AMPA=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_12730367}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12730367 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_12730367}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[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 Sat May 3 04:34:35 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 07:10:26 2008'' |
Revision as of 04:10, 28 July 2008
Template:STRUCTURE 1p1w
Crystal structure of the GluR2 ligand-binding core (S1S2J) with the L483Y and L650T mutations and in complex with AMPA
Template:ABSTRACT PUBMED 12730367
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 Mon Jul 28 07:10:26 2008
