View source for 8fpg


==GluA2 flip Q isoform of AMPA receptor in complex with gain-of-function TARP gamma-2, with 10mM CaCl2, 150mM NaCl, 1mM MgCl2, 330uM CTZ, and 100uM CNQX (Closed-CaNaMg)==
<StructureSection load='8fpg' size='340' side='right'caption='[[8fpg]], [[Resolution|resolution]] 2.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fpg]] is a 8 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=8FPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FPG 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]] 2.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=8fpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fpg OCA], [https://pdbe.org/8fpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fpg RCSB], [https://www.ebi.ac.uk/pdbsum/8fpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fpg 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/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).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid receptors (AMPARs) are cation-selective ion channels that mediate most fast excitatory neurotransmission in the brain. Although their gating mechanism has been studied extensively, understanding how cations traverse the pore has remained elusive. Here we investigated putative ion and water densities in the open pore of Ca(2+)-permeable AMPARs (rat GRIA2 flip-Q isoform) at 2.3-2.6 A resolution. We show that the ion permeation pathway attains an extracellular Ca(2+) binding site (site-G) when the channel gate moves into the open configuration. Site-G is highly selective for Ca(2+) over Na(+), favoring the movement of Ca(2+) into the selectivity filter of the pore. Seizure-related N619K mutation, adjacent to site-G, promotes channel opening but attenuates Ca(2+) binding and thus diminishes Ca(2+) permeability. Our work identifies the importance of site-G, which coordinates with the Q/R site of the selectivity filter to ensure the preferential transport of Ca(2+) through the channel pore.

The open gate of the AMPA receptor forms a Ca(2+) binding site critical in regulating ion transport.,Nakagawa T, Wang XT, Miguez-Cabello FJ, Bowie D Nat Struct Mol Biol. 2024 Apr;31(4):688-700. doi: 10.1038/s41594-024-01228-3. , Epub 2024 Feb 26. PMID:38409505<ref>PMID:38409505</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8fpg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Nakagawa T]]