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| | <StructureSection load='5w0x' size='340' side='right'caption='[[5w0x]], [[Resolution|resolution]] 2.72Å' scene=''> | | <StructureSection load='5w0x' size='340' side='right'caption='[[5w0x]], [[Resolution|resolution]] 2.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5w0x]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5W0X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5w0x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5W0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5W0X FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.717Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tiprl ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=5w0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0x OCA], [http://pdbe.org/5w0x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5w0x RCSB], [http://www.ebi.ac.uk/pdbsum/5w0x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0x 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=5w0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5w0x OCA], [https://pdbe.org/5w0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5w0x RCSB], [https://www.ebi.ac.uk/pdbsum/5w0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5w0x ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIPRL_MOUSE TIPRL_MOUSE]] May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AFX phosphorylated on Ser-140 (gamma-H2AFX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity).[UniProtKB:O75663] | + | [https://www.uniprot.org/uniprot/TIPRL_MOUSE TIPRL_MOUSE] May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AFX phosphorylated on Ser-140 (gamma-H2AFX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity).[UniProtKB:O75663] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Li, J]] | + | [[Category: Li J]] |
| - | [[Category: Satyshur, K]] | + | [[Category: Satyshur K]] |
| - | [[Category: Wu, C]] | + | [[Category: Wu C]] |
| - | [[Category: Xing, Y]] | + | [[Category: Xing Y]] |
| - | [[Category: Zheng, A]] | + | [[Category: Zheng A]] |
| - | [[Category: Butterfly-like fold protein phosphotase 2a regulator]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
TIPRL_MOUSE May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. Acts as negative regulator of serine/threonine-protein phosphatase 4 probably by inhibiting the formation of the active PPP4C:PPP4R2 complex; the function is proposed to implicate it in DNA damage response by promoting H2AFX phosphorylated on Ser-140 (gamma-H2AFX). May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair (By similarity).[UniProtKB:O75663]
Publication Abstract from PubMed
Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site. TIPRL also makes unusual wobble contacts with the scaffold subunit, allowing TIPRL, but not the overlapping regulatory subunits, to tolerate disease-associated PP2A mutations, resulting in reduced holoenzyme assembly and enhanced inactivation of mutant PP2A. Strikingly, TIPRL and the latency chaperone, alpha4, coordinate to disassemble active holoenzymes into latent PP2A, strictly controlled by methylation. Our study reveals a mechanism for methylation-responsive inactivation and holoenzyme disassembly, illustrating the complexity of regulation/signaling, dynamic complex disassembly, and disease mutations in cancer and intellectual disability.
Methylation-regulated decommissioning of multimeric PP2A complexes.,Wu CG, Zheng A, Jiang L, Rowse M, Stanevich V, Chen H, Li Y, Satyshur KA, Johnson B, Gu TJ, Liu Z, Xing Y Nat Commun. 2017 Dec 22;8(1):2272. doi: 10.1038/s41467-017-02405-3. PMID:29273778[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wu CG, Zheng A, Jiang L, Rowse M, Stanevich V, Chen H, Li Y, Satyshur KA, Johnson B, Gu TJ, Liu Z, Xing Y. Methylation-regulated decommissioning of multimeric PP2A complexes. Nat Commun. 2017 Dec 22;8(1):2272. doi: 10.1038/s41467-017-02405-3. PMID:29273778 doi:http://dx.doi.org/10.1038/s41467-017-02405-3
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