View source for 6fqj


==GluA2(flop) G724C ligand binding core dimer bound to ZK200775 at 2.50 Angstrom resolution==
<StructureSection load='6fqj' size='340' side='right'caption='[[6fqj]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6fqj]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FQJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FQJ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZK1:{[7-MORPHOLIN-4-YL-2,3-DIOXO-6-(TRIFLUOROMETHYL)-3,4-DIHYDROQUINOXALIN-1(2H)-YL]METHYL}PHOSPHONIC+ACID'>ZK1</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gria2, Glur2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fqj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqj OCA], [http://pdbe.org/6fqj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fqj RCSB], [http://www.ebi.ac.uk/pdbsum/6fqj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqj ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Desensitization is a canonical property of ligand-gated ion channels, causing progressive current decline in the continued presence of agonist. AMPA-type glutamate receptors (AMPARs), which mediate fast excitatory signaling throughout the brain, exhibit profound desensitization. Recent cryo-EM studies of AMPAR assemblies show their ion channels to be closed in the desensitized state. Here we present evidence that homomeric Q/R-edited AMPARs still allow ions to flow when the receptors are desensitized. GluA2(R) expressed alone, or with auxiliary subunits (gamma-2, gamma-8 or GSG1L), generates large fractional steady-state currents and anomalous current-variance relationships. Our results from fluctuation analysis, single-channel recording, and kinetic modeling, suggest that the steady-state current is mediated predominantly by conducting desensitized receptors. When combined with crystallography this unique functional readout of a hitherto silent state enabled us to examine cross-linked cysteine mutants to probe the conformation of the desensitized ligand binding domain of functioning AMPAR complexes.

Homomeric GluA2(R) AMPA receptors can conduct when desensitized.,Coombs ID, Soto D, McGee TP, Gold MG, Farrant M, Cull-Candy SG Nat Commun. 2019 Sep 20;10(1):4312. doi: 10.1038/s41467-019-12280-9. PMID:31541113<ref>PMID:31541113</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6fqj" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Large Structures]]
[[Category: Coombs, I D]]
[[Category: Cull-Candy, S G]]
[[Category: Farrant, M F]]
[[Category: Gold, M G]]
[[Category: Soto, D]]
[[Category: Ampar receptor]]
[[Category: Competitive antagonist]]
[[Category: Cross-linked dimer]]
[[Category: Ligand binding domain]]
[[Category: Membrane protein]]