6pus - Revision history

OCA at 09:27, 20 March 2024

OCA — Wed, 20 Mar 2024 09:27:23 GMT

←Older revision		Revision as of 09:27, 20 March 2024
Line 3:		Line 3:
	<SX load='6pus' size='340' side='right' viewer='molstar' caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>		<SX load='6pus' size='340' side='right' viewer='molstar' caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6PUS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pus]] is a 4 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=6PUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6PUS FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>~~, ~~<scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 3.7Å</td></tr>
-	<tr id='~~gene~~'><td class="sblockLbl"><b>[[~~Gene~~\|~~Gene~~:]]</b></td><td class="sblockDat">~~TRPM2, EREG1, KNP3, LTRPC2, TRPC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode~~=~~Info&srchmode~~=5~~&id~~=~~9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6pus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pus OCA], [~~http~~://pdbe.org/6pus PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6pus RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6pus PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6pus 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=6pus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pus OCA], [https://pdbe.org/6pus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6pus RCSB], [https://www.ebi.ac.uk/pdbsum/6pus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6pus ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/TRPM2_HUMAN TRPM2_HUMAN]] Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606).[UniProtKB:Q91YD4]<ref>PMID:11385575</ref> <ref>PMID:11509734</ref> <ref>PMID:11804595</ref> <ref>PMID:11960981</ref> <ref>PMID:12594222</ref> <ref>PMID:15561722</ref> <ref>PMID:16601673</ref> <ref>PMID:19171771</ref> <ref>PMID:19454650</ref> <ref>PMID:20650899</ref> <ref>PMID:20660597</ref> <ref>PMID:22493272</ref> <ref>PMID:25562606</ref> <ref>PMID:25918360</ref> <ref>PMID:27068538</ref> <ref>PMID:27383051</ref> Isoform 2: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose.<ref>PMID:11960981</ref> Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.<ref>PMID:12594222</ref>	+	[https://www.uniprot.org/uniprot/TRPM2_HUMAN TRPM2_HUMAN] Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606).[UniProtKB:Q91YD4]<ref>PMID:11385575</ref> <ref>PMID:11509734</ref> <ref>PMID:11804595</ref> <ref>PMID:11960981</ref> <ref>PMID:12594222</ref> <ref>PMID:15561722</ref> <ref>PMID:16601673</ref> <ref>PMID:19171771</ref> <ref>PMID:19454650</ref> <ref>PMID:20650899</ref> <ref>PMID:20660597</ref> <ref>PMID:22493272</ref> <ref>PMID:25562606</ref> <ref>PMID:25918360</ref> <ref>PMID:27068538</ref> <ref>PMID:27383051</ref> Isoform 2: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose.<ref>PMID:11960981</ref> Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.<ref>PMID:12594222</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca(2+) and ADP ribose (ADPR), an NAD(+)-metabolite produced under oxidative stress and neurodegenerative conditions, suggests a role in neurological disorders. We provide a central concept between triple-site ligand binding and the channel gating of human TRPM2. We show consecutive structural rearrangements and channel activation of TRPM2 induced by binding of ADPR in two indispensable locations, and the binding of Ca(2+) in the transmembrane domain. The 8-Br-cADPR-an antagonist of cADPR-binds only to the MHR1/2 domain and inhibits TRPM2 by stabilizing the channel in an apo-like conformation. We conclude that MHR1/2 acts as a orthostatic ligand-binding site for TRPM2. The NUDT9-H domain binds to a second ADPR to assist channel activation in vertebrates, but not necessary in invertebrates. Our work provides insights into the gating mechanism of human TRPM2 and its pharmacology.	+
-		+
-	Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel.,Huang Y, Roth B, Lu W, Du J Elife. 2019 Sep 12;8. pii: 50175. doi: 10.7554/eLife.50175. PMID:31513012<ref>PMID:31513012</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 6pus" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Du, J]]	+	[[Category: Du J]]
-	[[Category: Huang, Y]]	+	[[Category: Huang Y]]
-	[[Category: Lu, W]]	+	[[Category: Lu W]]
-	~~[[Category: Adpr]]~~	+
-	~~[[Category: Calcium]]~~	+
-	~~[[Category: Transport protein]]~~	+
-	~~[[Category: Trpm2 channel~~]]	+

OCA at 04:37, 11 April 2020

OCA — Sat, 11 Apr 2020 04:37:10 GMT

←Older revision		Revision as of 04:37, 11 April 2020
Line 3:		Line 3:
	<SX load='6pus' size='340' side='right' viewer='molstar' caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>		<SX load='6pus' size='340' side='right' viewer='molstar' caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6PUS FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6PUS FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRPM2, EREG1, KNP3, LTRPC2, TRPC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRPM2, EREG1, KNP3, LTRPC2, TRPC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6pus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pus OCA], [http://pdbe.org/6pus PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pus RCSB], [http://www.ebi.ac.uk/pdbsum/6pus PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pus ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6pus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pus OCA], [http://pdbe.org/6pus PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pus RCSB], [http://www.ebi.ac.uk/pdbsum/6pus PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pus ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 23:27, 6 March 2020

OCA — Fri, 06 Mar 2020 23:27:04 GMT

←Older revision		Revision as of 23:27, 6 March 2020
Line 1:		Line 1:

	==Human TRPM2 bound to ADPR and calcium==		==Human TRPM2 bound to ADPR and calcium==
-	<~~StructureSection~~ load='6pus' size='340' side='right'caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>	+	<SX load='6pus' size='340' side='right' viewer='molstar' caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PUS FirstGlance]. <br>		<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PUS FirstGlance]. <br>
Line 22:		Line 22:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 12:34, 18 December 2019

OCA — Wed, 18 Dec 2019 12:34:11 GMT

←Older revision		Revision as of 12:34, 18 December 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6pus is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Human TRPM2 bound to ADPR and calcium==
		+	<StructureSection load='6pus' size='340' side='right'caption='[[6pus]], [[Resolution\|resolution]] 3.70Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6pus]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6PUS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6PUS FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=APR:ADENOSINE-5-DIPHOSPHORIBOSE'>APR</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">TRPM2, EREG1, KNP3, LTRPC2, TRPC7 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6pus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6pus OCA], [http://pdbe.org/6pus PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6pus RCSB], [http://www.ebi.ac.uk/pdbsum/6pus PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6pus ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/TRPM2_HUMAN TRPM2_HUMAN]] Isoform 1: Nonselective, voltage-independent cation channel that mediates Na(+) and Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels (PubMed:11960981, PubMed:12594222, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:20660597, PubMed:27383051, PubMed:27068538). Extracellular calcium passes through the channel and increases channel activity by binding to the cytoplasmic domain and stabilizing the channel in an open conformation (PubMed:19171771). Also contributes to Ca(2+) release from intracellular stores in response to ADP-ribose (PubMed:19454650). Plays a role in numerous processes that involve signaling via intracellular Ca(2+) levels (Probable). Besides, mediates the release of lysosomal Zn(2+) stores in response to reactive oxygen species, leading to increased cytosolic Zn(2+) levels (PubMed:25562606, PubMed:27068538). Activated by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Activated by intracellular ADP-ribose, beta-NAD (NAD(+)) and similar compounds, and by oxidative stress caused by reactive oxygen or nitrogen species (PubMed:11960981, PubMed:11385575, PubMed:11509734, PubMed:11804595, PubMed:15561722, PubMed:16601673, PubMed:19171771, PubMed:27383051, PubMed:27068538). The precise physiological activators are under debate; the true, physiological activators may be ADP-ribose and ADP-ribose-2'-phosphate (PubMed:20650899, PubMed:25918360). Activation by ADP-ribose and beta-NAD is strongly increased by moderate heat (35 to 40 degrees Celsius) (PubMed:16601673). Likewise, reactive oxygen species lower the threshold for activation by moderate heat (37 degrees Celsius) (PubMed:22493272). Plays a role in mediating behavorial and physiological responses to moderate heat and thereby contributes to body temperature homeostasis. Plays a role in insulin secretion, a process that requires increased cytoplasmic Ca(2+) levels (By similarity). Required for normal IFNG and cytokine secretion and normal innate immune immunity in response to bacterial infection. Required for normal phagocytosis and cytokine release by macrophages exposed to zymosan (in vitro). Plays a role in dendritic cell differentiation and maturation, and in dendritic cell chemotaxis via its role in regulating cytoplasmic Ca(2+) levels (By similarity). Plays a role in the regulation of the reorganization of the actin cytoskeleton and filopodia formation in response to reactive oxygen species via its role in increasing cytoplasmic Ca(2+) and Zn(2+) levels (PubMed:27068538). Confers susceptibility to cell death following oxidative stress (PubMed:12594222, PubMed:25562606).[UniProtKB:Q91YD4]<ref>PMID:11385575</ref> <ref>PMID:11509734</ref> <ref>PMID:11804595</ref> <ref>PMID:11960981</ref> <ref>PMID:12594222</ref> <ref>PMID:15561722</ref> <ref>PMID:16601673</ref> <ref>PMID:19171771</ref> <ref>PMID:19454650</ref> <ref>PMID:20650899</ref> <ref>PMID:20660597</ref> <ref>PMID:22493272</ref> <ref>PMID:25562606</ref> <ref>PMID:25918360</ref> <ref>PMID:27068538</ref> <ref>PMID:27383051</ref> Isoform 2: Lacks cation channel activity. Does not mediate cation transport in response to oxidative stress or ADP-ribose.<ref>PMID:11960981</ref> Isoform 3: Lacks cation channel activity and negatively regulates the channel activity of isoform 1. Negatively regulates susceptibility to cell death in reposponse to oxidative stress.<ref>PMID:12594222</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	TRPM2 is critically involved in diverse physiological processes including core temperature sensing, apoptosis, and immune response. TRPM2's activation by Ca(2+) and ADP ribose (ADPR), an NAD(+)-metabolite produced under oxidative stress and neurodegenerative conditions, suggests a role in neurological disorders. We provide a central concept between triple-site ligand binding and the channel gating of human TRPM2. We show consecutive structural rearrangements and channel activation of TRPM2 induced by binding of ADPR in two indispensable locations, and the binding of Ca(2+) in the transmembrane domain. The 8-Br-cADPR-an antagonist of cADPR-binds only to the MHR1/2 domain and inhibits TRPM2 by stabilizing the channel in an apo-like conformation. We conclude that MHR1/2 acts as a orthostatic ligand-binding site for TRPM2. The NUDT9-H domain binds to a second ADPR to assist channel activation in vertebrates, but not necessary in invertebrates. Our work provides insights into the gating mechanism of human TRPM2 and its pharmacology.

-	~~Authors~~:	+	Ligand recognition and gating mechanism through three ligand-binding sites of human TRPM2 channel.,Huang Y, Roth B, Lu W, Du J Elife. 2019 Sep 12;8. pii: 50175. doi: 10.7554/eLife.50175. PMID:31513012<ref>PMID:31513012</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 6pus" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
		+	[[Category: Du, J]]
		+	[[Category: Huang, Y]]
		+	[[Category: Lu, W]]
		+	[[Category: Adpr]]
		+	[[Category: Calcium]]
		+	[[Category: Transport protein]]
		+	[[Category: Trpm2 channel]]

OCA at 04:44, 31 July 2019

OCA — Wed, 31 Jul 2019 04:44:51 GMT

←Older revision		Revision as of 04:44, 31 July 2019
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 24 Jul 2019 04:37:17 GMT

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

←Older revision

Revision as of 04:37, 24 July 2019

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

OCA — Wed, 24 Jul 2019 04:37:16 GMT

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

New page

'''Unreleased structure'''

The entry 6pus is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]