7soy: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7soy]] 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=7SOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SOY FirstGlance]. <br> | <table><tr><td colspan='2'>[[7soy]] 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=7SOY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SOY FirstGlance]. <br> | ||
</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=7soy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7soy OCA], [https://pdbe.org/7soy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7soy RCSB], [https://www.ebi.ac.uk/pdbsum/7soy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7soy ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4Å</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=7soy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7soy OCA], [https://pdbe.org/7soy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7soy RCSB], [https://www.ebi.ac.uk/pdbsum/7soy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7soy ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/2AAA_HUMAN 2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.<ref>PMID:16580887</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme-PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores. | Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme-PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores. | ||
Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition.,Li Y, Balakrishnan VK, Rowse M, Wu CG, Bravos AP, Yadav VK, Ivarsson Y, Strack S, Novikova IV, Xing Y Elife. 2022 Aug 4;11 | Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition.,Li Y, Balakrishnan VK, Rowse M, Wu CG, Bravos AP, Yadav VK, Ivarsson Y, Strack S, Novikova IV, Xing Y Elife. 2022 Aug 4;11:e79736. doi: 10.7554/eLife.79736. PMID:35924897<ref>PMID:35924897</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7soy" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7soy" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||