View source for 7qhh


==Desensitized state of GluA1/2 AMPA receptor in complex with TARP-gamma 8 (TMD-LBD)==
<StructureSection load='7qhh' size='340' side='right'caption='[[7qhh]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7qhh]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QHH 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]] 3.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=79N:(2S)-2,3-DIHYDROXYPROPYL+(7Z)-HEXADEC-7-ENOATE'>79N</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PAM:PALMITOLEIC+ACID'>PAM</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=7qhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qhh OCA], [https://pdbe.org/7qhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qhh RCSB], [https://www.ebi.ac.uk/pdbsum/7qhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qhh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GRIA1_RAT GRIA1_RAT] Ionotropic glutamate receptor. 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:16793768</ref> <ref>PMID:19265014</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor's ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-gamma8 complex, in both open and desensitized states (at 3.5 A), reveal state-selective engagement of the LBDs by the large TARP-gamma8 loop ('beta1'), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance.

Mechanisms underlying TARP modulation of the GluA1/2-gamma8 AMPA receptor.,Herguedas B, Kohegyi BK, Dohrke JN, Watson JF, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH Nat Commun. 2022 Feb 8;13(1):734. doi: 10.1038/s41467-022-28404-7. PMID:35136046<ref>PMID:35136046</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7qhh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Dohrke JN]]
[[Category: Greger IH]]
[[Category: Herguedas B]]
[[Category: Ho H]]
[[Category: Kohegyi B]]
[[Category: Krieger JM]]
[[Category: Lape R]]
[[Category: Shaikh S]]
[[Category: Watson JF]]
[[Category: Zhang D]]