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| | <StructureSection load='5d9g' size='340' side='right'caption='[[5d9g]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='5d9g' size='340' side='right'caption='[[5d9g]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d9g]] 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=5D9G OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D9G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d9g]] 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=5D9G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D9G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</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=MSE:SELENOMETHIONINE'>MSE</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=5d9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d9g OCA], [https://pdbe.org/5d9g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d9g RCSB], [https://www.ebi.ac.uk/pdbsum/5d9g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d9g ProSAT]</span></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=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=5d9g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d9g OCA], [http://pdbe.org/5d9g PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d9g RCSB], [http://www.ebi.ac.uk/pdbsum/5d9g PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d9g ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TIPRL_HUMAN TIPRL_HUMAN]] May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair.<ref>PMID:17384681</ref> | + | [https://www.uniprot.org/uniprot/TIPRL_HUMAN TIPRL_HUMAN] May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair.<ref>PMID:17384681</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Aparicio, R]] | + | [[Category: Aparicio R]] |
| - | [[Category: Brandao-Neto, J]] | + | [[Category: Brandao-Neto J]] |
| - | [[Category: Pereira, H M]] | + | [[Category: Pereira HM]] |
| - | [[Category: Sandy, J]] | + | [[Category: Sandy J]] |
| - | [[Category: Scorsato, V]] | + | [[Category: Scorsato V]] |
| - | [[Category: Smetana, J H.C]] | + | [[Category: Smetana JHC]] |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Protein binding tip41-like family pp2a]]
| + | |
| Structural highlights
Function
TIPRL_HUMAN May be a allosteric regulator of serine/threonine-protein phosphatase 2A (PP2A). Isoform 1 inhibits catalytic activity of the PP2A(D) core complex in vitro. The PP2A(C):TIPRL complex does not show phosphatase activity. May play a role in the regulation of ATM/ATR signaling pathway controlling DNA replication and repair.[1]
Publication Abstract from PubMed
TOR signaling pathway regulator-like (TIPRL) is a regulatory protein which inhibits the catalytic subunits of Type 2A phosphatases. Several cellular contexts have been proposed for TIPRL, such as regulation of mTOR signaling, inhibition of apoptosis and biogenesis and recycling of PP2A, however, the underlying molecular mechanism is still poorly understood. We have solved the crystal structure of human TIPRL at 2.15 A resolution. The structure is a novel fold organized around a central core of antiparallel beta-sheet, showing an N-terminal alpha/beta region at one of its surfaces and a conserved cleft at the opposite surface. Inside this cleft, we found a peptide derived from TEV-mediated cleavage of the affinity tag. We show by mutagenesis, pulldown and hydrogen/deuterium exchange mass spectrometry that this peptide is a mimic for the conserved C-terminal tail of PP2A, an important region of the phosphatase which regulates holoenzyme assembly, and TIPRL preferentially binds the unmodified version of the PP2A-tail mimetic peptide DYFL compared to its tyrosine-phosphorylated version. A docking model of the TIPRL-PP2Ac complex suggests that TIPRL blocks the phosphatase's active site, providing a structural framework for the function of TIPRL in PP2A inhibition.
Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus.,Scorsato V, Lima TB, Righetto GL, Zanchin NI, Brandao-Neto J, Sandy J, Pereira HD, Ferrari AJ, Gozzo FC, Smetana JH, Aparicio R Sci Rep. 2016 Aug 4;6:30813. doi: 10.1038/srep30813. PMID:27489114[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ McConnell JL, Gomez RJ, McCorvey LR, Law BK, Wadzinski BE. Identification of a PP2A-interacting protein that functions as a negative regulator of phosphatase activity in the ATM/ATR signaling pathway. Oncogene. 2007 Sep 6;26(41):6021-30. Epub 2007 Mar 26. PMID:17384681 doi:http://dx.doi.org/10.1038/sj.onc.1210406
- ↑ Scorsato V, Lima TB, Righetto GL, Zanchin NI, Brandao-Neto J, Sandy J, Pereira HD, Ferrari AJ, Gozzo FC, Smetana JH, Aparicio R. Crystal structure of the human Tip41 orthologue, TIPRL, reveals a novel fold and a binding site for the PP2Ac C-terminus. Sci Rep. 2016 Aug 4;6:30813. doi: 10.1038/srep30813. PMID:27489114 doi:http://dx.doi.org/10.1038/srep30813
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