6li1 - Revision history

OCA at 07:06, 3 April 2024

2024-04-03T07:06:24Z

←Older revision		Revision as of 07:06, 3 April 2024
Line 3:		Line 3:
	<StructureSection load='6li1' size='340' side='right'caption='[[6li1]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='6li1' size='340' side='right'caption='[[6li1]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6li1]] is a 1 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Desvh Desvh~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6LI1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6li1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Desulfovibrio_vulgaris_str._Hildenborough Desulfovibrio vulgaris str. Hildenborough] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LI1 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.9Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GPR52 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=882 DESVH])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6li1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li1 OCA], [~~http~~://pdbe.org/6li1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6li1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6li1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6li1 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=6li1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li1 OCA], [https://pdbe.org/6li1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6li1 RCSB], [https://www.ebi.ac.uk/pdbsum/6li1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6li1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/GPR52_HUMAN GPR52_HUMAN]] Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).<ref>PMID:24587241</ref> <ref>PMID:25738228</ref>	+	[https://www.uniprot.org/uniprot/FLAV_DESVH FLAV_DESVH] Low-potential electron donor to a number of redox enzymes.[https://www.uniprot.org/uniprot/GPR52_HUMAN GPR52_HUMAN] Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).<ref>PMID:24587241</ref> <ref>PMID:25738228</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several psychiatric disorders(1,2). Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric Gs protein(2), but it is unclear how GPR52 and Gs couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a Gs-coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR52(3). A fully active state is achieved when Gs is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52.	+
-		+
-	Structural basis of ligand recognition and self-activation of orphan GPR52.,Lin X, Li M, Wang N, Wu Y, Luo Z, Guo S, Han GW, Li S, Yue Y, Wei X, Xie X, Chen Y, Zhao S, Wu J, Lei M, Xu F Nature. 2020 Feb 19. pii: 10.1038/s41586-020-2019-0. doi:, 10.1038/s41586-020-2019-0. PMID:32076264<ref>PMID:32076264</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6li1" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Desvh~~]]	+	[[Category: Desulfovibrio vulgaris str. Hildenborough]]
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Han~~, G W~~]]	+	[[Category: Han GW]]
-	[[Category: Lin, X]]	+	[[Category: Lin X]]
-	[[Category: Luo~~, Z P~~]]	+	[[Category: Luo ZP]]
-	[[Category: Xu, F]]	+	[[Category: Xu F]]
-	~~[[Category: Apo form]]~~	+
-	~~[[Category: Class some]]~~	+
-	~~[[Category: Flavodoxin]]~~	+
-	~~[[Category: Human gpr52 receptor]]~~	+
-	~~[[Category: Lcp]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Orphan gpcr~~]]	+

OCA at 07:11, 4 March 2020

2020-03-04T07:11:54Z

←Older revision		Revision as of 07:11, 4 March 2020
Line 3:		Line 3:
	<StructureSection load='6li1' size='340' side='right'caption='[[6li1]], [[Resolution\|resolution]] 2.90Å' scene=''>		<StructureSection load='6li1' size='340' side='right'caption='[[6li1]], [[Resolution\|resolution]] 2.90Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6li1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LI1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6li1]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Desvh Desvh]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LI1 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GPR52 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=882 DESVH])</td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6li1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li1 OCA], [http://pdbe.org/6li1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6li1 RCSB], [http://www.ebi.ac.uk/pdbsum/6li1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6li1 ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6li1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li1 OCA], [http://pdbe.org/6li1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6li1 RCSB], [http://www.ebi.ac.uk/pdbsum/6li1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6li1 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/GPR52_HUMAN GPR52_HUMAN]] Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).<ref>PMID:24587241</ref> <ref>PMID:25738228</ref>		[[http://www.uniprot.org/uniprot/GPR52_HUMAN GPR52_HUMAN]] Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).<ref>PMID:24587241</ref> <ref>PMID:25738228</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	GPR52 is a class-A orphan G-protein-coupled receptor that is highly expressed in the brain and represents a promising therapeutic target for the treatment of Huntington's disease and several psychiatric disorders(1,2). Pathological malfunction of GPR52 signalling occurs primarily through the heterotrimeric Gs protein(2), but it is unclear how GPR52 and Gs couple for signal transduction and whether a native ligand or other activating input is required. Here we present the high-resolution structures of human GPR52 in three states: a ligand-free state, a Gs-coupled self-activation state and a potential allosteric ligand-bound state. Together, our structures reveal that extracellular loop 2 occupies the orthosteric binding pocket and operates as a built-in agonist, conferring an intrinsically high level of basal activity to GPR52(3). A fully active state is achieved when Gs is coupled to GPR52 in the absence of an external agonist. The receptor also features a side pocket for ligand binding. These insights into the structure and function of GPR52 could improve our understanding of other self-activated GPCRs, enable the identification of endogenous and tool ligands, and guide drug discovery efforts that target GPR52.
		+
		+	Structural basis of ligand recognition and self-activation of orphan GPR52.,Lin X, Li M, Wang N, Wu Y, Luo Z, Guo S, Han GW, Li S, Yue Y, Wei X, Xie X, Chen Y, Zhao S, Wu J, Lei M, Xu F Nature. 2020 Feb 19. pii: 10.1038/s41586-020-2019-0. doi:, 10.1038/s41586-020-2019-0. PMID:32076264<ref>PMID:32076264</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6li1" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Desvh]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Han, G W]]		[[Category: Han, G W]]

OCA at 09:14, 26 February 2020

2020-02-26T09:14:40Z

←Older revision		Revision as of 09:14, 26 February 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6li1 is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of GPR52 ligand free form with flavodoxin fusion==
-		+	<StructureSection load='6li1' size='340' side='right'caption='[[6li1]], [[Resolution\|resolution]] 2.90Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6li1]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LI1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LI1 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6li1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6li1 OCA], [http://pdbe.org/6li1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6li1 RCSB], [http://www.ebi.ac.uk/pdbsum/6li1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6li1 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GPR52_HUMAN GPR52_HUMAN]] Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).<ref>PMID:24587241</ref> <ref>PMID:25738228</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Han, G W]]
		+	[[Category: Lin, X]]
		+	[[Category: Luo, Z P]]
		+	[[Category: Xu, F]]
		+	[[Category: Apo form]]
		+	[[Category: Class some]]
		+	[[Category: Flavodoxin]]
		+	[[Category: Human gpr52 receptor]]
		+	[[Category: Lcp]]
		+	[[Category: Membrane protein]]
		+	[[Category: Orphan gpcr]]

OCA at 12:58, 29 January 2020

2020-01-29T12:58:23Z

←Older revision		Revision as of 12:58, 29 January 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6li1 is ON HOLD	+	The entry 6li1 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6li1" [edit=sysop:move=sysop]

2019-12-18T05:42:27Z

Protected "6li1" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:42, 18 December 2019

OCA: New page: '''Unreleased structure''' The entry 6li1 is ON HOLD Authors: Description: Category: Unreleased Structures

2019-12-18T05:42:26Z

New page: '''Unreleased structure''' The entry 6li1 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6li1 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]