3b7d
From Proteopedia
(New page: 200px<br /><applet load="3b7d" size="350" color="white" frame="true" align="right" spinBox="true" caption="3b7d, resolution 2.50Å" /> '''Crystal structure of...) |
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==Overview== | ==Overview== | ||
| - | Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione | + | Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: CSMP, Center | + | [[Category: CSMP, Center for Structures of Membrane Proteins.]] |
| - | [[Category: Hays, F | + | [[Category: Hays, F A.]] |
[[Category: CNI]] | [[Category: CNI]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
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[[Category: transport]] | [[Category: transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:03:50 2008'' |
Revision as of 17:03, 21 February 2008
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Crystal structure of the GLUR2 ligand binding core (HS1S2J) in complex with CNQX at 2.5 A resolution
Overview
Quinoxalinedione compounds such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) are the most commonly used alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists. However, we find that in the presence of transmembrane AMPA receptor regulatory proteins (TARPs), which are AMPA receptor auxiliary subunits, CNQX acts as a partial agonist. CNQX induced small depolarizing currents in neurons of the central nervous system, and reconstitution of this agonist activity required coexpression of TARPs. A crystal structure of CNQX bound to the TARP-less AMPA receptor ligand-binding domain showed that, although CNQX induces partial domain closure, this movement is not transduced into linker separation, suggesting that TARPs may increase agonist efficacy by strengthening the coupling between domain closure and channel opening. Our results demonstrate that the presence of an auxiliary subunit can determine whether a compound functions as an agonist or antagonist.
About this Structure
3B7D is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists., Menuz K, Stroud RM, Nicoll RA, Hays FA, Science. 2007 Nov 2;318(5851):815-7. PMID:17975069
Page seeded by OCA on Thu Feb 21 19:03:50 2008
Categories: Rattus norvegicus | Single protein | CSMP, Center for Structures of Membrane Proteins. | Hays, F A. | CNI | Alternative splicing | Cell junction | Center for structures of membrane proteins | Cnqx | Csmp | Glycoprotein | Ion transport | Ionic channel | Lipoprotein | Palmitate | Phosphorylation | Postsynaptic cell membrane | Protein structure initiative | Psi-2 | Receptor | Rna editing | S1s2 | Structural genomics | Synapse | Transmembrane | Transport
