7m6p - Revision history

OCA at 18:54, 7 September 2022

OCA — Wed, 07 Sep 2022 18:54:06 GMT

←Older revision		Revision as of 18:54, 7 September 2022
Line 9:		Line 9:
	== 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;">
		+	== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7m6p" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:46, 7 September 2022

OCA — Wed, 07 Sep 2022 16:46:49 GMT

←Older revision		Revision as of 16:46, 7 September 2022
Line 3:		Line 3:
	<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]], [[Resolution\|resolution]] 3.28Å' scene=''>		<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]], [[Resolution\|resolution]] 3.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7m6p]] is a 5 chain structure. 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>	+	<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='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>		</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>		<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>		</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;">~~	+
-	~~== 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.	+
-		+
-	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>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7m6p" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__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~~]]	+

OCA at 05:07, 10 August 2022

OCA — Wed, 10 Aug 2022 05:07:34 GMT

←Older revision		Revision as of 05:07, 10 August 2022
Line 1:		Line 1:

-	==~~1mG~~==	+	==Full length alpha1 Glycine receptor in presence of 1mM Glycine==
-	<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]]' scene=''>	+	<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]], [[Resolution\|resolution]] 3.28Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>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>	+	<table><tr><td colspan='2'>[[7m6p]] is a 5 chain structure. 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='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>	+	</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>		</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 ==
		+	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.
		+
		+	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>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7m6p" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[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]]

OCA at 04:50, 3 August 2022

OCA — Wed, 03 Aug 2022 04:50:17 GMT

←Older revision		Revision as of 04:50, 3 August 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 7m6p ~~is ON HOLD until Paper Publication~~	+	==1mG==
-		+	<StructureSection load='7m6p' size='340' side='right'caption='[[7m6p]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>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>
-	~~Description~~:	+	</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>
-	[[Category: ~~Unreleased~~ Structures]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Chakrapani S]]
		+	[[Category: Kumar A]]

OCA at 04:55, 2 March 2022

OCA — Wed, 02 Mar 2022 04:55:36 GMT

←Older revision		Revision as of 04:55, 2 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7m6p is ON HOLD	+	The entry 7m6p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 05:15, 27 January 2022

OCA — Thu, 27 Jan 2022 05:15:11 GMT

←Older revision		Revision as of 05:15, 27 January 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7m6p is ON HOLD ~~until Paper Publication~~	+	The entry 7m6p is ON HOLD

	Authors:		Authors:

OCA at 11:45, 29 December 2021

OCA — Wed, 29 Dec 2021 11:45:29 GMT

←Older revision		Revision as of 11:45, 29 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7m6p is ON HOLD	+	The entry 7m6p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA at 04:59, 1 December 2021

OCA — Wed, 01 Dec 2021 04:59:14 GMT

←Older revision		Revision as of 04:59, 1 December 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7m6p is ON HOLD ~~until Paper Publication~~	+	The entry 7m6p is ON HOLD

	Authors:		Authors:

OCA at 11:03, 9 June 2021

OCA — Wed, 09 Jun 2021 11:03:52 GMT

←Older revision		Revision as of 11:03, 9 June 2021
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7m6p is ON HOLD	+	The entry 7m6p is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7m6p" [edit=sysop:move=sysop]

OCA — Wed, 31 Mar 2021 09:26:28 GMT

Protected "7m6p" [edit=sysop:move=sysop]

←Older revision

Revision as of 09:26, 31 March 2021