View source for 7ryz


==Structure of the complex of LBD-TMD part of AMPA receptor GluA2 with auxiliary subunit GSG1L bound to agonist quisqualate==
<StructureSection load='7ryz' size='340' side='right'caption='[[7ryz]], [[Resolution|resolution]] 4.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ryz]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RYZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RYZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=QUS:(S)-2-AMINO-3-(3,5-DIOXO-[1,2,4]OXADIAZOLIDIN-2-YL)-PROPIONIC+ACID'>QUS</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=7ryz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ryz OCA], [https://pdbe.org/7ryz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ryz RCSB], [https://www.ebi.ac.uk/pdbsum/7ryz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ryz ProSAT]</span></td></tr>
</table>
== 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>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
AMPA receptors (AMPARs) mediate the majority of excitatory neurotransmission. Their surface expression, trafficking, gating, and pharmacology are regulated by auxiliary subunits. Of the two types of TARP auxiliary subunits, type I TARPs assume activating roles, while type II TARPs serve suppressive functions. We present cryo-EM structures of GluA2 AMPAR in complex with type II TARP gamma5, which reduces steady-state currents, increases single-channel conductance, and slows recovery from desensitization. Regulation of AMPAR function depends on its ligand-binding domain (LBD) interaction with the gamma5 head domain. GluA2-gamma5 complex shows maximum stoichiometry of two TARPs per AMPAR tetramer, being different from type I TARPs but reminiscent of the auxiliary subunit GSG1L. Desensitization of both GluA2-GSG1L and GluA2-gamma5 complexes is accompanied by rupture of LBD dimer interface, while GluA2-gamma5 but not GluA2-GSG1L LBD dimers remain two-fold symmetric. Different structural architectures and desensitization mechanisms of complexes with auxiliary subunits endow AMPARs with broad functional capabilities.

Structure and desensitization of AMPA receptor complexes with type II TARP gamma5 and GSG1L.,Klykov O, Gangwar SP, Yelshanskaya MV, Yen L, Sobolevsky AI Mol Cell. 2021 Dec 2;81(23):4771-4783.e7. doi: 10.1016/j.molcel.2021.09.030. Epub, 2021 Oct 21. PMID:34678168<ref>PMID:34678168</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ryz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Gangwar, S P]]
[[Category: Klykov, O V]]
[[Category: Sobolevsky, A I]]
[[Category: Yelshanskaya, M V]]
[[Category: Ampa receptor]]
[[Category: Gsg1l]]
[[Category: Ion channel]]
[[Category: Membrane protein]]
[[Category: Neurotransmission]]
[[Category: Synapse]]