7m6m

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:33, 21 November 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 3: Line 3:
<StructureSection load='7m6m' size='340' side='right'caption='[[7m6m]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
<StructureSection load='7m6m' size='340' side='right'caption='[[7m6m]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[7m6m]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7M6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M6M FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[7m6m]] 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=7M6M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M6M FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TCI:(6AR,10AR)-6,6,9-TRIMETHYL-3-PENTYL-6A,7,8,10A-TETRAHYDRO-6H-BENZO[C]CHROMEN-1-OL'>TCI</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.09&#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=TCI:(6AR,10AR)-6,6,9-TRIMETHYL-3-PENTYL-6A,7,8,10A-TETRAHYDRO-6H-BENZO[C]CHROMEN-1-OL'>TCI</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=7m6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6m OCA], [https://pdbe.org/7m6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6m RCSB], [https://www.ebi.ac.uk/pdbsum/7m6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6m 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=7m6m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m6m OCA], [https://pdbe.org/7m6m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m6m RCSB], [https://www.ebi.ac.uk/pdbsum/7m6m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m6m ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>
+
[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;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
-
Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Glycine receptors (GlyRs) are key players in mediating fast inhibitory neurotransmission at these synapses. While previous high-resolution structures have provided insights into the molecular architecture of GlyR, several mechanistic questions pertaining to channel function are still unanswered. Here, we present Cryo-EM structures of the full-length GlyR protein complex reconstituted into lipid nanodiscs that are captured in the unliganded (closed), glycine-bound (open and desensitized), and allosteric modulator-bound conformations. A comparison of these states reveals global conformational changes underlying GlyR channel gating and modulation. The functional state assignments were validated by molecular dynamics simulations, and the observed permeation events are in agreement with the anion selectivity and conductance of GlyR. These studies provide the structural basis for gating, ion selectivity, and single-channel conductance properties of GlyR in a lipid environment.
+
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.
-
Mechanisms of activation and desensitization of full-length glycine receptor in lipid nanodiscs.,Kumar A, Basak S, Rao S, Gicheru Y, Mayer ML, Sansom MSP, Chakrapani S Nat Commun. 2020 Jul 27;11(1):3752. doi: 10.1038/s41467-020-17364-5. PMID:32719334<ref>PMID:32719334</ref>
+
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>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Line 22: Line 23:
__TOC__
__TOC__
</StructureSection>
</StructureSection>
 +
[[Category: Danio rerio]]
[[Category: Large Structures]]
[[Category: Large Structures]]
-
[[Category: Chakrapani, S]]
+
[[Category: Chakrapani S]]
-
[[Category: Kumar, A]]
+
[[Category: Kumar A]]
-
[[Category: Glycine receptor recombinant protein]]
+
-
[[Category: Ions ligands receptor]]
+
-
[[Category: Membrane protein]]
+

Current revision

Full length alpha1 Glycine receptor in presence of 32uM Tetrahydrocannabinol

PDB ID 7m6m

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7m6m"
Personal tools