4ut3

From Proteopedia

(Difference between revisions)

Revision as of 07:37, 29 March 2023

X-ray structure of the human PP1 gamma catalytic subunit treated with hydrogen peroxide

Structural highlights

4ut3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PP1G_HUMAN Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase.^[1] ^[2]

Publication Abstract from PubMed

Phosphorylation of translation initiation factor 2alpha (eIF2alpha) attenuates global protein synthesis but enhances translation of activating transcription factor 4 (ATF4) and is a crucial evolutionarily conserved adaptive pathway during cellular stresses. The serine-threonine protein phosphatase 1 (PP1) deactivates this pathway whereas prolonging eIF2alpha phosphorylation enhances cell survival. Here, we show that the reactive oxygen species-generating NADPH oxidase-4 (Nox4) is induced downstream of ATF4, binds to a PP1-targeting subunit GADD34 at the endoplasmic reticulum, and inhibits PP1 activity to increase eIF2alpha phosphorylation and ATF4 levels. Other PP1 targets distant from the endoplasmic reticulum are unaffected, indicating a spatially confined inhibition of the phosphatase. PP1 inhibition involves metal center oxidation rather than the thiol oxidation that underlies redox inhibition of protein tyrosine phosphatases. We show that this Nox4-regulated pathway robustly enhances cell survival and has a physiologic role in heart ischemia-reperfusion and acute kidney injury. This work uncovers a novel redox signaling pathway, involving Nox4-GADD34 interaction and a targeted oxidative inactivation of the PP1 metal center, that sustains eIF2alpha phosphorylation to protect tissues under stress.

Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2alpha-mediated stress signaling.,Santos CX, Hafstad AD, Beretta M, Zhang M, Molenaar C, Kopec J, Fotinou D, Murray TV, Cobb AM, Martin D, Zeh Silva M, Anilkumar N, Schroder K, Shanahan CM, Brewer AC, Brandes RP, Blanc E, Parsons M, Belousov V, Cammack R, Hider RC, Steiner RA, Shah AM EMBO J. 2016 Feb 1;35(3):319-34. doi: 10.15252/embj.201592394. Epub 2016 Jan 7. PMID:26742780^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Djouder N, Metzler SC, Schmidt A, Wirbelauer C, Gstaiger M, Aebersold R, Hess D, Krek W. S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes activates a negative feedback program that counters S6K1 survival signaling. Mol Cell. 2007 Oct 12;28(1):28-40. PMID:17936702 doi:http://dx.doi.org/10.1016/j.molcel.2007.08.010
↑ Lee JH, You J, Dobrota E, Skalnik DG. Identification and characterization of a novel human PP1 phosphatase complex. J Biol Chem. 2010 Aug 6;285(32):24466-76. doi: 10.1074/jbc.M110.109801. Epub 2010, Jun 1. PMID:20516061 doi:http://dx.doi.org/10.1074/jbc.M110.109801
↑ Santos CX, Hafstad AD, Beretta M, Zhang M, Molenaar C, Kopec J, Fotinou D, Murray TV, Cobb AM, Martin D, Zeh Silva M, Anilkumar N, Schroder K, Shanahan CM, Brewer AC, Brandes RP, Blanc E, Parsons M, Belousov V, Cammack R, Hider RC, Steiner RA, Shah AM. Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2alpha-mediated stress signaling. EMBO J. 2016 Feb 1;35(3):319-34. doi: 10.15252/embj.201592394. Epub 2016 Jan 7. PMID:26742780 doi:http://dx.doi.org/10.15252/embj.201592394

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ut3"

@@ Line 3: / Line 3: @@
 <StructureSection load='4ut3' size='340' side='right'caption='[[4ut3]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ut3]] is a 2 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=4UT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UT3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ut3]] is a 2 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=4UT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UT3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</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=4ut3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ut3 OCA], [https://pdbe.org/4ut3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ut3 RCSB], [https://www.ebi.ac.uk/pdbsum/4ut3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ut3 ProSAT]</span></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ut2|4ut2]]</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ut3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ut3 OCA], [http://pdbe.org/4ut3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ut3 RCSB], [http://www.ebi.ac.uk/pdbsum/4ut3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ut3 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/PP1G_HUMAN PP1G_HUMAN]] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase.<ref>PMID:17936702</ref> <ref>PMID:20516061</ref>
+[https://www.uniprot.org/uniprot/PP1G_HUMAN PP1G_HUMAN] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase.<ref>PMID:17936702</ref> <ref>PMID:20516061</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 18: @@
 </div>
 <div class="pdbe-citations 4ut3" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Phosphoprotein phosphatase]]
+[[Category: Fotinou D]]
-[[Category: Fotinou, D]]
+[[Category: Kopec J]]
-[[Category: Kopec, J]]
+[[Category: Steiner RA]]
-[[Category: Silva, M Zeh]]
+[[Category: Zeh Silva M]]
-[[Category: Steiner, R A]]
-[[Category: Enzyme activation]]
-[[Category: Hydrolase]]
-[[Category: Metal center]]
-[[Category: Metalloprotein]]
-[[Category: Protein phosphatase 1]]

4ut3

From Proteopedia

Revision as of 07:37, 29 March 2023

X-ray structure of the human PP1 gamma catalytic subunit treated with hydrogen peroxide

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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