View source for 5weo


==Activated GluA2 complex bound to glutamate, cyclothiazide, and STZ in digitonin==
<SX load='5weo' size='340' side='right' viewer='molstar' caption='[[5weo]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5weo]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WEO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WEO FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5weo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5weo OCA], [https://pdbe.org/5weo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5weo RCSB], [https://www.ebi.ac.uk/pdbsum/5weo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5weo ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/CCG2_MOUSE CCG2_MOUSE] Note=Defects in Cacng2 cause the stargazer (stg) phenotype. Stg mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear.
== Function ==
[https://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> [https://www.uniprot.org/uniprot/CCG2_MOUSE CCG2_MOUSE] Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state (By similarity).
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== Publication Abstract from PubMed ==
AMPA-subtype ionotropic glutamate receptors mediate fast excitatory neurotransmission throughout the central nervous system. Gated by the neurotransmitter glutamate, AMPA receptors are critical for synaptic strength and dysregulation of AMPA receptor-mediated signalling is linked to numerous neurological diseases. Here, we use cryo-electron microscopy to solve the structures of AMPA receptor-auxiliary subunit complexes in the apo, antagonist and agonist-bound states and elucidate the iris-like mechanism of ion channel opening. The ion channel selectivity filter is formed by the extended portions of the re-entrant M2 loops, while the helical portions of M2 contribute to extensive hydrophobic interfaces between AMPA receptor subunits in the ion channel. We show how the permeation pathway changes upon channel opening and identify conformational changes throughout the entire AMPA receptor that accompany activation and desensitization. Our findings provide a framework for understanding gating across the family of ionotropic glutamate receptors and the role of AMPA receptors in excitatory neurotransmission.

Channel opening and gating mechanism in AMPA-subtype glutamate receptors.,Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI Nature. 2017 Jul 24. doi: 10.1038/nature23479. PMID:28737760<ref>PMID:28737760</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5weo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Frank J]]
[[Category: Grassucci RA]]
[[Category: Sobolevsky AI]]
[[Category: Twomey EC]]
[[Category: Yelshanskaya MV]]