7tnj: Difference between revisions

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<StructureSection load='7tnj' size='340' side='right'caption='[[7tnj]], [[Resolution|resolution]] 4.02&Aring;' scene=''>
<StructureSection load='7tnj' size='340' side='right'caption='[[7tnj]], [[Resolution|resolution]] 4.02&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7tnj]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNJ FirstGlance]. <br>
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TNJ FirstGlance]. <br>
</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></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.02&#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></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=7tnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnj OCA], [https://pdbe.org/7tnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnj RCSB], [https://www.ebi.ac.uk/pdbsum/7tnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnj ProSAT]</span></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=7tnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tnj OCA], [https://pdbe.org/7tnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tnj RCSB], [https://www.ebi.ac.uk/pdbsum/7tnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tnj ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels that open their pores in response to binding of the agonist glutamate(1-3). An ionic current through a single iGluR channel shows up to four discrete conductance levels (O1-O4)(4-6). Higher conductance levels have been associated with an increased number of agonist molecules bound to four individual ligand-binding domains (LBDs)(6-10). Here we determine structures of a synaptic complex of AMPA-subtype iGluR and the auxiliary subunit gamma2 in non-desensitizing conditions with various occupancy of the LBDs by glutamate. We show that glutamate binds to LBDs of subunits B and D only after it is already bound to at least the same number of LBDs that belong to subunits A and C. Our structures combined with single-channel recordings, molecular dynamics simulations and machine-learning analysis suggest that channel opening requires agonist binding to at least two LBDs. Conversely, agonist binding to all four LBDs does not guarantee maximal channel conductance and favours subconductance states O1 and O2, with O3 and O4 being rare and not captured structurally. The lack of subunit independence and low efficiency coupling of glutamate binding to channel opening underlie the gating of synaptic complexes to submaximal conductance levels, which provide a potential for upregulation of synaptic activity.


Opening of glutamate receptor channel to subconductance levels.,Yelshanskaya MV, Patel DS, Kottke CM, Kurnikova MG, Sobolevsky AI Nature. 2022 Apr 20. pii: 10.1038/s41586-022-04637-w. doi:, 10.1038/s41586-022-04637-w. PMID:35444281<ref>PMID:35444281</ref>
==See Also==
 
*[[Glutamate receptor 3D structures|Glutamate receptor 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7tnj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Sobolevsky, A I]]
[[Category: Sobolevsky AI]]
[[Category: Yelshanskaya, M V]]
[[Category: Yelshanskaya MV]]
[[Category: Agonist]]
[[Category: Ampa]]
[[Category: Complex]]
[[Category: Cryo-em]]
[[Category: Gating]]
[[Category: Glutamate]]
[[Category: Iglur]]
[[Category: Membrane protein]]
[[Category: Opening]]
[[Category: Positive allosteric modulator]]
[[Category: Stargazin]]
[[Category: Subconductance level]]

Latest revision as of 11:41, 30 October 2024

Complex NNNN of AMPA-subtype iGluR GluA2 in complex with auxiliary subunit gamma2 (Stargazin) at low glutamate concentration (20 uM) in the presence of cyclothiazide (100 uM)

7tnj, resolution 4.02Å

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