7qal - Revision history

OCA at 18:56, 7 September 2022

OCA — Wed, 07 Sep 2022 18:56:36 GMT

←Older revision		Revision as of 18:56, 7 September 2022
Line 8:		Line 8:
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN]] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref>		[[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN]] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The intramembrane protease PARL acts as a crucial mitochondrial safeguard by cleaving the mitophagy regulators PINK1 and PGAM5. Depending on the stress level, PGAM5 can either stimulate cell survival or cell death. In contrast to PINK1, which is constantly cleaved in healthy mitochondria and only active when the inner mitochondrial membrane is depolarized, PGAM5 processing is inversely regulated. However, determinants of PGAM5 that indicate it as a conditional substrate for PARL have not been rigorously investigated, and it is unclear how uncoupling the mitochondrial membrane potential affects its processing compared to that of PINK1. Here, we show that several polar transmembrane residues in PGAM5 distant from the cleavage site serve as key determinants for its PARL-catalyzed cleavage. Our NMR analysis indicates that a short N-terminal amphipathic helix, followed by a kink and a C-terminal transmembrane helix harboring the scissile peptide bond, are key for a productive interaction with PARL. Furthermore, we also show that PGAM5 is stably inserted into the inner mitochondrial membrane until uncoupling the membrane potential triggers its disassembly into monomers, which are then cleaved by PARL. In conclusion, we propose a model in which PGAM5 is slowly processed by PARL-catalyzed cleavage that is influenced by multiple hierarchical substrate features, including a membrane potential-dependent oligomeric switch.
		+
		+	Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.,Siebert V, Silber M, Heuten E, Muhle-Goll C, Lemberg MK J Biol Chem. 2022 Jul 31:102321. doi: 10.1016/j.jbc.2022.102321. PMID:35921890<ref>PMID:35921890</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qal" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 16:48, 7 September 2022

OCA — Wed, 07 Sep 2022 16:48:19 GMT

←Older revision		Revision as of 16:48, 7 September 2022
Line 1:		Line 1:

	==Three-dimensional structure of the PGAM5 C12L mutant TMD==		==Three-dimensional structure of the PGAM5 C12L mutant TMD==
-	<StructureSection load='7qal' size='340' side='right'caption='[[7qal~~]], [[NMR_Ensembles_of_Models \| 20 NMR models~~]]' scene=''>	+	<StructureSection load='7qal' size='340' side='right'caption='[[7qal]]' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7qal]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7qal]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAL FirstGlance]. <br>
-	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=7qal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qal OCA], [https://pdbe.org/7qal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qal RCSB], [https://www.ebi.ac.uk/pdbsum/7qal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qal 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=7qal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qal OCA], [https://pdbe.org/7qal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qal RCSB], [https://www.ebi.ac.uk/pdbsum/7qal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qal ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN]] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref>	+	[[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN]] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref>
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The intramembrane protease PARL acts as a crucial mitochondrial safeguard by cleaving the mitophagy regulators PINK1 and PGAM5. Depending on the stress level, PGAM5 can either stimulate cell survival or cell death. In contrast to PINK1, which is constantly cleaved in healthy mitochondria and only active when the inner mitochondrial membrane is depolarized, PGAM5 processing is inversely regulated. However, determinants of PGAM5 that indicate it as a conditional substrate for PARL have not been rigorously investigated, and it is unclear how uncoupling the mitochondrial membrane potential affects its processing compared to that of PINK1. Here, we show that several polar transmembrane residues in PGAM5 distant from the cleavage site serve as key determinants for its PARL-catalyzed cleavage. Our NMR analysis indicates that a short N-terminal amphipathic helix, followed by a kink and a C-terminal transmembrane helix harboring the scissile peptide bond, are key for a productive interaction with PARL. Furthermore, we also show that PGAM5 is stably inserted into the inner mitochondrial membrane until uncoupling the membrane potential triggers its disassembly into monomers, which are then cleaved by PARL. In conclusion, we propose a model in which PGAM5 is slowly processed by PARL-catalyzed cleavage that is influenced by multiple hierarchical substrate features, including a membrane potential-dependent oligomeric switch.	+
-		+
-	Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.,Siebert V, Silber M, Heuten E, Muhle-Goll C, Lemberg MK J Biol Chem. 2022 Jul 31:102321. doi: 10.1016/j.jbc.2022.102321. PMID:35921890<ref>PMID:35921890</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 7qal" style="background-color:#fffaf0;"></div~~>	+
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Phosphoprotein phosphatase]]~~	+	[[Category: Muhle-Goll C]]
-	[[Category: Muhle-Goll, C]]	+	[[Category: Silber M]]
-	[[Category: Silber, M]]	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Mitochondria]]~~	+
-	~~[[Category: Parl~~]]	+

OCA at 06:38, 18 August 2022

OCA — Thu, 18 Aug 2022 06:38:22 GMT

←Older revision		Revision as of 06:38, 18 August 2022
Line 1:		Line 1:

	==Three-dimensional structure of the PGAM5 C12L mutant TMD==		==Three-dimensional structure of the PGAM5 C12L mutant TMD==
-	<StructureSection load='7qal' size='340' side='right'caption='[[7qal]]' scene=''>	+	<StructureSection load='7qal' size='340' side='right'caption='[[7qal]], [[NMR_Ensembles_of_Models \| 20 NMR models]]' 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=7QAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAL FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7qal]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAL 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=7qal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qal OCA], [https://pdbe.org/7qal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qal RCSB], [https://www.ebi.ac.uk/pdbsum/7qal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qal ProSAT]</span></td></tr>	+	</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </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=7qal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qal OCA], [https://pdbe.org/7qal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qal RCSB], [https://www.ebi.ac.uk/pdbsum/7qal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qal ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/PGAM5_HUMAN PGAM5_HUMAN]] Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.<ref>PMID:18387606</ref> <ref>PMID:19590015</ref> <ref>PMID:22265414</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The intramembrane protease PARL acts as a crucial mitochondrial safeguard by cleaving the mitophagy regulators PINK1 and PGAM5. Depending on the stress level, PGAM5 can either stimulate cell survival or cell death. In contrast to PINK1, which is constantly cleaved in healthy mitochondria and only active when the inner mitochondrial membrane is depolarized, PGAM5 processing is inversely regulated. However, determinants of PGAM5 that indicate it as a conditional substrate for PARL have not been rigorously investigated, and it is unclear how uncoupling the mitochondrial membrane potential affects its processing compared to that of PINK1. Here, we show that several polar transmembrane residues in PGAM5 distant from the cleavage site serve as key determinants for its PARL-catalyzed cleavage. Our NMR analysis indicates that a short N-terminal amphipathic helix, followed by a kink and a C-terminal transmembrane helix harboring the scissile peptide bond, are key for a productive interaction with PARL. Furthermore, we also show that PGAM5 is stably inserted into the inner mitochondrial membrane until uncoupling the membrane potential triggers its disassembly into monomers, which are then cleaved by PARL. In conclusion, we propose a model in which PGAM5 is slowly processed by PARL-catalyzed cleavage that is influenced by multiple hierarchical substrate features, including a membrane potential-dependent oligomeric switch.
		+
		+	Cleavage of mitochondrial homeostasis regulator PGAM5 by the intramembrane protease PARL is governed by transmembrane helix dynamics and oligomeric state.,Siebert V, Silber M, Heuten E, Muhle-Goll C, Lemberg MK J Biol Chem. 2022 Jul 31:102321. doi: 10.1016/j.jbc.2022.102321. PMID:35921890<ref>PMID:35921890</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7qal" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Muhle-Goll C]]	+	[[Category: Phosphoprotein phosphatase]]
-	[[Category: Silber M]]	+	[[Category: Muhle-Goll, C]]
		+	[[Category: Silber, M]]
		+	[[Category: Membrane protein]]
		+	[[Category: Mitochondria]]
		+	[[Category: Parl]]

OCA at 12:48, 4 May 2022

OCA — Wed, 04 May 2022 12:48:44 GMT

←Older revision		Revision as of 12:48, 4 May 2022
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 7qal is ON HOLD~~	+	==Three-dimensional structure of the PGAM5 C12L mutant TMD==
-		+	<StructureSection load='7qal' size='340' side='right'caption='[[7qal]]' scene=''>
-	~~Authors: Silber, M., Muhle-Goll, C.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7QAL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QAL FirstGlance]. <br>
-	~~Description:~~ Three-dimensional structure of the PGAM5 C12L mutant TMD	+	</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=7qal FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qal OCA], [https://pdbe.org/7qal PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qal RCSB], [https://www.ebi.ac.uk/pdbsum/7qal PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qal ProSAT]</span></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	</table>
-	[[~~Category~~: ~~Silber~~, M]]	+	__TOC__
-	[[Category: Muhle-Goll, C]]	+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Muhle-Goll C]]
		+	[[Category: Silber M]]

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

OCA — Wed, 24 Nov 2021 10:52:13 GMT

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

←Older revision

Revision as of 10:52, 24 November 2021

OCA: New page: '''Unreleased structure''' The entry 7qal is ON HOLD Authors: Silber, M., Muhle-Goll, C. Description: Three-dimensional structure of the PGAM5 C12L mutant TMD [[Category: Unreleased St...

OCA — Wed, 24 Nov 2021 10:52:11 GMT

New page: '''Unreleased structure''' The entry 7qal is ON HOLD Authors: Silber, M., Muhle-Goll, C. Description: Three-dimensional structure of the PGAM5 C12L mutant TMD [[Category: Unreleased St...

New page

'''Unreleased structure'''

The entry 7qal is ON HOLD

Authors: Silber, M., Muhle-Goll, C.

Description: Three-dimensional structure of the PGAM5 C12L mutant TMD
[[Category: Unreleased Structures]]
[[Category: Silber, M]]
[[Category: Muhle-Goll, C]]