5swf: Difference between revisions
New page: '''Unreleased structure''' The entry 5swf is ON HOLD Authors: Page, R., Wang, X., Bajaj, R., Peti, W. Description: The structure of the PP2A B56 subunit double phosphorylated BubR1 com... |
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The | ==The structure of the PP2A B56 subunit double phosphorylated BubR1 complex== | ||
<StructureSection load='5swf' size='340' side='right'caption='[[5swf]], [[Resolution|resolution]] 2.82Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5swf]] 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=5SWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SWF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.818Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</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=5swf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5swf OCA], [https://pdbe.org/5swf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5swf RCSB], [https://www.ebi.ac.uk/pdbsum/5swf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5swf ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/2A5G_HUMAN 2A5G_HUMAN] The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.<ref>PMID:16456541</ref> <ref>PMID:17245430</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Specific interactions between proteins govern essential physiological processes including signaling. Many enzymes, especially the family of serine/threonine phosphatases (PSPs: PP1, PP2A, and PP2B/calcineurin/CN), recruit substrates and regulatory proteins by binding short linear motifs (SLiMs), short sequences found within intrinsically disordered regions that mediate specific protein-protein interactions. While tremendous progress had been made in identifying where and how SLiMs bind PSPs, especially PP1 and CN, essentially nothing is known about how SLiMs bind PP2A, a validated cancer drug target. Here we describe three structures of a PP2A-SLiM interaction (B56:pS-RepoMan, B56:pS-BubR1, and B56:pSpS-BubR1), show that this PP2A-specific SLiM is defined as LSPIxE, and then use these data to discover scores of likely PP2A regulators and substrates. Together, these data provide a powerful approach not only for dissecting PP2A interaction networks in cells but also for targeting PP2A diseases, such as cancer. | |||
Expanding the PP2A Interactome by Defining a B56-Specific SLiM.,Wang X, Bajaj R, Bollen M, Peti W, Page R Structure. 2016 Dec 6;24(12):2174-2181. doi: 10.1016/j.str.2016.09.010. Epub 2016, Oct 27. PMID:27998540<ref>PMID:27998540</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5swf" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Peti | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Bajaj R]] | |||
[[Category: Page R]] | |||
[[Category: Peti W]] | |||
[[Category: Wang X]] | |||
Latest revision as of 15:48, 4 October 2023
The structure of the PP2A B56 subunit double phosphorylated BubR1 complexThe structure of the PP2A B56 subunit double phosphorylated BubR1 complex
Structural highlights
Function2A5G_HUMAN The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. The PP2A-PPP2R5C holoenzyme may specifically dephosphorylate and activate TP53 and play a role in DNA damage-induced inhibition of cell proliferation. PP2A-PPP2R5C may also regulate the ERK signaling pathway through ERK dephosphorylation.[1] [2] Publication Abstract from PubMedSpecific interactions between proteins govern essential physiological processes including signaling. Many enzymes, especially the family of serine/threonine phosphatases (PSPs: PP1, PP2A, and PP2B/calcineurin/CN), recruit substrates and regulatory proteins by binding short linear motifs (SLiMs), short sequences found within intrinsically disordered regions that mediate specific protein-protein interactions. While tremendous progress had been made in identifying where and how SLiMs bind PSPs, especially PP1 and CN, essentially nothing is known about how SLiMs bind PP2A, a validated cancer drug target. Here we describe three structures of a PP2A-SLiM interaction (B56:pS-RepoMan, B56:pS-BubR1, and B56:pSpS-BubR1), show that this PP2A-specific SLiM is defined as LSPIxE, and then use these data to discover scores of likely PP2A regulators and substrates. Together, these data provide a powerful approach not only for dissecting PP2A interaction networks in cells but also for targeting PP2A diseases, such as cancer. Expanding the PP2A Interactome by Defining a B56-Specific SLiM.,Wang X, Bajaj R, Bollen M, Peti W, Page R Structure. 2016 Dec 6;24(12):2174-2181. doi: 10.1016/j.str.2016.09.010. Epub 2016, Oct 27. PMID:27998540[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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