View source for 8u89


==The structure of the PP2A-B56Delta holoenzyme mutant - E197K==
<StructureSection load='8u89' size='340' side='right'caption='[[8u89]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8u89]] 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=8U89 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8U89 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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=8u89 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8u89 OCA], [https://pdbe.org/8u89 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8u89 RCSB], [https://www.ebi.ac.uk/pdbsum/8u89 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8u89 ProSAT]</span></td></tr>
</table>
== 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;">
== Publication Abstract from PubMed ==
Intrinsically disordered regions (IDR) and short linear motifs (SLiMs) play pivotal roles in the intricate signaling networks governed by phosphatases and kinases. B56delta (encoded by PPP2R5D) is a regulatory subunit of protein phosphatase 2A (PP2A) with long IDRs that harbor a substrate-mimicking SLiM and multiple phosphorylation sites. De novo missense mutations in PPP2R5D cause intellectual disabilities (ID), macrocephaly, Parkinsonism, and a broad range of neurological symptoms. Our single-particle cryo-EM structures of the PP2A-B56delta holoenzyme reveal that the long, disordered arms at the B56delta termini fold against each other and the holoenzyme core. This architecture suppresses both the phosphatase active site and the substrate-binding protein groove, thereby stabilizing the enzyme in a closed latent form with dual autoinhibition. The resulting interface spans over 190 A and harbors unfavorable contacts, activation phosphorylation sites, and nearly all residues with ID-associated mutations. Our studies suggest that this dynamic interface is coupled to an allosteric network responsive to phosphorylation and altered globally by mutations. Furthermore, we found that ID mutations increase the holoenzyme activity and perturb the phosphorylation rates, and the severe variants significantly increase the mitotic duration and error rates compared to the normal variant.

B56delta long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations.,Wu CG, Balakrishnan VK, Merrill RA, Parihar PS, Konovolov K, Chen YC, Xu Z, Wei H, Sundaresan R, Cui Q, Wadzinski BE, Swingle MR, Musiyenko A, Chung WK, Honkanen RE, Suzuki A, Huang X, Strack S, Xing Y Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2310727120. doi: , 10.1073/pnas.2310727120. Epub 2023 Dec 27. PMID:38150499<ref>PMID:38150499</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8u89" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Wu CG]]
[[Category: Xing Y]]