This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1p1n
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:1p1n.jpg|left|200px]] | + | [[Image:1p1n.jpg|left|200px]] |
| - | + | ||
| - | '''GluR2 Ligand Binding Core (S1S2J) Mutant L650T in Complex with Kainate''' | + | {{Structure |
| + | |PDB= 1p1n |SIZE=350|CAPTION= <scene name='initialview01'>1p1n</scene>, resolution 1.6Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= GRIA2 OR GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus]) | ||
| + | }} | ||
| + | |||
| + | '''GluR2 Ligand Binding Core (S1S2J) Mutant L650T in Complex with Kainate''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 1P1N is a [ | + | 1P1N 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=1P1N 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]] | ||
| Line 19: | Line 28: | ||
[[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 13:18:40 2008'' |
Revision as of 11:18, 20 March 2008
| |||||||
| , resolution 1.6Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | GRIA2 OR GLUR2 (Rattus norvegicus) | ||||||
| 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
Page seeded by OCA on Thu Mar 20 13:18:40 2008
