View source for 7m6p


==Full length alpha1 Glycine receptor in presence of 1mM Glycine==
<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]], [[Resolution|resolution]] 3.28&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7m6p]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M6P 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]] 3.28&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GLY:GLYCINE'>GLY</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=7m6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6p OCA], [https://pdbe.org/7m6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6p RCSB], [https://www.ebi.ac.uk/pdbsum/7m6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6p ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GLRA1_DANRE GLRA1_DANRE] Glycine receptors are ligand-gated chloride channels. Channel opening is triggered by extracellular glycine (PubMed:10188956, PubMed:26344198). Plays an important role in the down-regulation of neuronal excitability. Contributes to the generation of inhibitory postsynaptic currents. Channel activity is potentiated by ethanol (By similarity).[UniProtKB:P23415]<ref>PMID:10188956</ref> <ref>PMID:26344198</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Nociception and motor coordination are critically governed by glycine receptor (GlyR) function at inhibitory synapses. Consequentially, GlyRs are attractive targets in the management of chronic pain and in the treatment of several neurological disorders. High-resolution mechanistic details of GlyR function and its modulation are just emerging. While it has been known that cannabinoids such as Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive constituent in marijuana, potentiate GlyR in the therapeutically relevant concentration range, the molecular mechanism underlying this effect is still not understood. Here, we present Cryo-EM structures of full-length GlyR reconstituted into lipid nanodisc in complex with THC under varying concentrations of glycine. The GlyR-THC complexes are captured in multiple conformational states that reveal the basis for THC-mediated potentiation, manifested as different extents of opening at the level of the channel pore. Taken together, these structural findings, combined with molecular dynamics simulations and functional analysis, provide insights into the potential THC binding site and the allosteric coupling to the channel pore.

Structural basis for cannabinoid-induced potentiation of alpha1-glycine receptors in lipid nanodiscs.,Kumar A, Kindig K, Rao S, Zaki AM, Basak S, Sansom MSP, Biggin PC, Chakrapani S Nat Commun. 2022 Aug 18;13(1):4862. doi: 10.1038/s41467-022-32594-5. PMID:35982060<ref>PMID:35982060</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7m6p" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Chakrapani S]]
[[Category: Kumar A]]