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| | ==Crystal Structure of Protein Phosphatase 2A (PP2A) and PP2A phosphatase activator (PTPA) complex with ATPgammaS== | | ==Crystal Structure of Protein Phosphatase 2A (PP2A) and PP2A phosphatase activator (PTPA) complex with ATPgammaS== |
| - | <StructureSection load='4lac' size='340' side='right' caption='[[4lac]], [[Resolution|resolution]] 2.82Å' scene=''> | + | <StructureSection load='4lac' size='340' side='right'caption='[[4lac]], [[Resolution|resolution]] 2.82Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lac]] is a 3 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=4LAC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LAC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lac]] is a 3 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=4LAC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LAC FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AGS:PHOSPHOTHIOPHOSPHORIC+ACID-ADENYLATE+ESTER'>AGS</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PP2A Catalytic Subunit C, PPP2R4, PTPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PP2A Phosphatase Activator ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PP2A Scaffold Subunit A, PPP2CA ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4lac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lac OCA], [https://pdbe.org/4lac PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lac RCSB], [https://www.ebi.ac.uk/pdbsum/4lac PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lac ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=4lac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lac OCA], [http://pdbe.org/4lac PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lac RCSB], [http://www.ebi.ac.uk/pdbsum/4lac PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lac ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTPA_HUMAN PTPA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.<ref>PMID:17333320</ref> <ref>PMID:16916641</ref> [[http://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref> | + | [https://www.uniprot.org/uniprot/PTPA_HUMAN PTPA_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.<ref>PMID:17333320</ref> <ref>PMID:16916641</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4lac" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4lac" style="background-color:#fffaf0;"></div> |
| - | | |
| - | ==See Also== | |
| - | *[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]] | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Guo, F]] | + | [[Category: Guo F]] |
| - | [[Category: Satyshur, K A]] | + | [[Category: Satyshur KA]] |
| - | [[Category: Stanevich, V]] | + | [[Category: Stanevich V]] |
| - | [[Category: Wlodarchak, N]] | + | [[Category: Wlodarchak N]] |
| - | [[Category: Xing, Y]] | + | [[Category: Xing Y]] |
| - | [[Category: Chaperone]]
| + | |
| - | [[Category: Hydrolase-signaling protein complex]]
| + | |
| - | [[Category: Pp2a]]
| + | |
| - | [[Category: Protein phosphatase]]
| + | |
| - | [[Category: Ptpa]]
| + | |
| - | [[Category: Signaling pathway regulation]]
| + | |
| Structural highlights
Function
PTPA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine-protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A.[1] [2]
Publication Abstract from PubMed
Proper activation of protein phosphatase 2A (PP2A) catalytic subunit is central for the complex PP2A regulation and is crucial for broad aspects of cellular function. The crystal structure of PP2A bound to PP2A phosphatase activator (PTPA) and ATPgammaS reveals that PTPA makes broad contacts with the structural elements surrounding the PP2A active site and the adenine moiety of ATP. PTPA-binding stabilizes the protein fold of apo-PP2A required for activation, and orients ATP phosphoryl groups to bind directly to the PP2A active site. This allows ATP to modulate the metal-binding preferences of the PP2A active site and utilize the PP2A active site for ATP hydrolysis. In vitro, ATP selectively and drastically enhances binding of endogenous catalytic metal ions, which requires ATP hydrolysis and is crucial for acquisition of pSer/Thr-specific phosphatase activity. Furthermore, both PP2A- and ATP-binding are required for PTPA function in cell proliferation and survival. Our results suggest novel mechanisms of PTPA in PP2A activation with structural economy and a unique ATP-binding pocket that could potentially serve as a specific therapeutic target.Cell Research advance online publication 8 October 2013; doi:10.1038/cr.2013.138.
Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone.,Guo F, Stanevich V, Wlodarchak N, Sengupta R, Jiang L, Satyshur KA, Xing Y Cell Res. 2013 Oct 8. doi: 10.1038/cr.2013.138. PMID:24100351[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Azam S, Drobetsky E, Ramotar D. Overexpression of the cis/trans isomerase PTPA triggers caspase 3-dependent apoptosis. Apoptosis. 2007 Jul;12(7):1243-55. PMID:17333320 doi:http://dx.doi.org/10.1007/s10495-006-0050-8
- ↑ Chao Y, Xing Y, Chen Y, Xu Y, Lin Z, Li Z, Jeffrey PD, Stock JB, Shi Y. Structure and mechanism of the phosphotyrosyl phosphatase activator. Mol Cell. 2006 Aug;23(4):535-46. PMID:16916641 doi:http://dx.doi.org/10.1016/j.molcel.2006.07.027
- ↑ Guo F, Stanevich V, Wlodarchak N, Sengupta R, Jiang L, Satyshur KA, Xing Y. Structural basis of PP2A activation by PTPA, an ATP-dependent activation chaperone. Cell Res. 2013 Oct 8. doi: 10.1038/cr.2013.138. PMID:24100351 doi:http://dx.doi.org/10.1038/cr.2013.138
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