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6fqk
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6fqk is ON HOLD until Paper Publication Authors: Coombs, I.D., Soto, D., Gold, M.G., Farrant, M.F., Cull-Candy, S.G. Description: GluA2(flop) S729C...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==GluA2(flop) S729C ligand binding core dimer bound to ZK200775 at 1.98 Angstrom resolution== | |
| + | <StructureSection load='6fqk' size='340' side='right'caption='[[6fqk]], [[Resolution|resolution]] 1.98Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6fqk]] is a 2 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=6FQK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FQK 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=6fqk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fqk OCA], [http://pdbe.org/6fqk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fqk RCSB], [http://www.ebi.ac.uk/pdbsum/6fqk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fqk 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6fqk" style="background-color:#fffaf0;"></div> |
| - | [[Category: Cull-Candy, S | + | |
| - | [[Category: Farrant, M | + | ==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: Soto, D]] | ||
| - | [[Category: | + | [[Category: Ampar receptor]] |
| + | [[Category: Competitive antagonist]] | ||
| + | [[Category: Cross-linked dimer]] | ||
| + | [[Category: Ligand binding domain]] | ||
| + | [[Category: Membrane protein]] | ||
Current revision
GluA2(flop) S729C ligand binding core dimer bound to ZK200775 at 1.98 Angstrom resolution
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