8dpg - Revision history

OCA at 12:03, 23 October 2024

2024-10-23T12:03:18Z

← Older revision		Revision as of 12:03, 23 October 2024
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[8dpg]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPG FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dpg]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91Q:3-[2-(dimethylamino)ethyl]-1~{H}-indol-4-ol'>91Q</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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]] 3.6Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=91Q:3-[2-(dimethylamino)ethyl]-1~{H}-indol-4-ol'>91Q</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg 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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/5HT2C_HUMAN 5HT2C_HUMAN]] G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.<ref>PMID:12970106</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:7895773</ref>		[https://www.uniprot.org/uniprot/5HT2C_HUMAN 5HT2C_HUMAN] G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.<ref>PMID:12970106</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:7895773</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
	RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The ~~5HT2C~~ serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These ~~5HT2C~~ isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state ~~5HT2C~~-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.		RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT(2C) serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT(2C) isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT(2C)-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.

	Molecular insights into the regulation of constitutive activity by RNA editing of ~~5HT2C~~ serotonin receptors.,Gumpper RH, Fay JF, Roth BL Cell Rep. 2022 Aug 16;40(7):111211. doi: 10.1016/j.celrep.2022.111211. PMID:35977511<ref>PMID:35977511</ref>		Molecular insights into the regulation of constitutive activity by RNA editing of 5HT(2C) serotonin receptors.,Gumpper RH, Fay JF, Roth BL Cell Rep. 2022 Aug 16;40(7):111211. doi: 10.1016/j.celrep.2022.111211. PMID:35977511<ref>PMID:35977511</ref>

	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
	<div class="pdbe-citations 8dpg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 8dpg" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Antibody 3D structures\|Antibody 3D structures]]
			*[[Transducin 3D structures\|Transducin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 19:55, 7 September 2022

2022-09-07T19:55:49Z

← Older revision		Revision as of 19:55, 7 September 2022
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	==Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to psilocin==		==Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to psilocin==
	<StructureSection load='8dpg' size='340' side='right'caption='[[8dpg]]' scene=''>		<StructureSection load='8dpg' size='340' side='right'caption='[[8dpg]], [[Resolution\|resolution]] 3.60Å' 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=8DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPG FirstGlance]. <br>		<table><tr><td colspan='2'>[[8dpg]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPG 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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg 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=91Q:3-[2-(dimethylamino)ethyl]-1~{H}-indol-4-ol'>91Q</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/5HT2C_HUMAN 5HT2C_HUMAN]] G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.<ref>PMID:12970106</ref> <ref>PMID:18703043</ref> <ref>PMID:19057895</ref> <ref>PMID:7895773</ref>
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			RNA editing is a process by which post-transcriptional changes of mRNA nucleotides alter protein function through modification of the amino acid content. The 5HT2C serotonin receptor, which undergoes 32 distinct RNA-editing events leading to 24 protein isoforms, is a notable example of this process. These 5HT2C isoforms display differences in constitutive activity, agonist/inverse agonist potencies, and efficacies. To elucidate the molecular mechanisms responsible for these effects of RNA editing, we present four active-state 5HT2C-transducer-coupled structures of three representative isoforms (INI, VGV, and VSV) with the selective drug lorcaserin (Belviq) and the classic psychedelic psilocin. We also provide a comprehensive analysis of agonist activation and constitutive activity across all 24 protein isoforms. Collectively, these findings reveal a unique hydrogen-bonding network located on intracellular loop 2 that is subject to RNA editing, which differentially affects GPCR constitutive and agonist signaling activities.

			Molecular insights into the regulation of constitutive activity by RNA editing of 5HT2C serotonin receptors.,Gumpper RH, Fay JF, Roth BL Cell Rep. 2022 Aug 16;40(7):111211. doi: 10.1016/j.celrep.2022.111211. PMID:35977511<ref>PMID:35977511</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 8dpg" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Fay JF]]		[[Category: Fay JF]]
	[[Category: Gumpper RH]]		[[Category: Gumpper RH]]
	[[Category: Roth BL]]		[[Category: Roth BL]]

OCA at 10:16, 31 August 2022

2022-08-31T10:16:10Z

← Older revision		Revision as of 10:16, 31 August 2022
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	====		==Cryo-EM structure of the 5HT2C receptor (INI isoform) bound to psilocin==
	<StructureSection load='8dpg' size='340' side='right'caption='[[8dpg]]' scene=''>		<StructureSection load='8dpg' size='340' side='right'caption='[[8dpg]]' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>		<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DPG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DPG 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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg ProSAT]</span></td></tr>		</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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg ProSAT]</span></td></tr>
	</table>		</table>
Line 9:		Line 9:
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~Z-disk~~]]		[[Category: Fay JF]]
			[[Category: Gumpper RH]]
			[[Category: Roth BL]]

OCA at 04:52, 25 August 2022

2022-08-25T04:52:53Z

← Older revision		Revision as of 04:52, 25 August 2022
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	~~'''Unreleased structure'''~~

	~~The entry~~ 8dpg is ~~ON HOLD~~		====
			<StructureSection load='8dpg' size='340' side='right'caption='[[8dpg]]' scene=''>
	~~Authors:~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= 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=8dpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dpg OCA], [https://pdbe.org/8dpg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dpg RCSB], [https://www.ebi.ac.uk/pdbsum/8dpg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dpg ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: Z-disk]]

OCA: Protected "8dpg" [edit=sysop:move=sysop]

2022-07-27T16:44:45Z

Protected "8dpg" [edit=sysop:move=sysop]

← Older revision	Revision as of 16:44, 27 July 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 8dpg is ON HOLD Authors: Description: Category: Unreleased Structures

2022-07-27T16:44:44Z

New page: '''Unreleased structure''' The entry 8dpg is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8dpg is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]