View source for 5kbt


==Cryo-EM structure of GluA2-1xSTZ complex at 6.4 Angstrom resolution==
<SX load='5kbt' size='340' side='right' viewer='molstar' caption='[[5kbt]], [[Resolution|resolution]] 6.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5kbt]] 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=5KBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5KBT 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]] 6.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5kbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5kbt OCA], [https://pdbe.org/5kbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5kbt RCSB], [https://www.ebi.ac.uk/pdbsum/5kbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5kbt 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 (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, gating, and pharmacology is tightly controlled by transmembrane AMPAR regulatory proteins (TARPs). Here, we used cryo-electron microscopy to elucidate the structural basis of AMPAR regulation by one of these auxiliary proteins, TARP gamma2, or stargazin (STZ). Our structures illuminate the variable interaction stoichiometry of the AMPAR-TARP complex, with one or two TARP molecules binding one tetrameric AMPAR. Analysis of the AMPAR-STZ binding interfaces suggests that electrostatic interactions between the extracellular domains of AMPAR and STZ play an important role in modulating AMPAR function through contact surfaces that are conserved across AMPARs and TARPs. We propose a model explaining how TARPs stabilize the activated state of AMPARs and how the interactions between AMPARs and their auxiliary proteins control fast excitatory synaptic transmission.

Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.,Twomey EC, Yelshanskaya MV, Grassucci RA, Frank J, Sobolevsky AI Science. 2016 Jul 1;353(6294):83-6. doi: 10.1126/science.aaf8411. PMID:27365450<ref>PMID:27365450</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
== References ==
<references/>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Frank J]]
[[Category: Grassucci RA]]
[[Category: Sobolevsky AI]]
[[Category: Twomey EC]]
[[Category: Yelshanskaya MV]]