View source for 6ghm


==Structure of PP1 alpha phosphatase bound to ASPP2==
<StructureSection load='6ghm' size='340' side='right' caption='[[6ghm]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ghm]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GHM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GHM FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=NHE:2-[N-CYCLOHEXYLAMINO]ETHANE+SULFONIC+ACID'>NHE</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></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=6ghm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ghm OCA], [http://pdbe.org/6ghm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ghm RCSB], [http://www.ebi.ac.uk/pdbsum/6ghm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ghm ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/PP1A_HUMAN PP1A_HUMAN]] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.<ref>PMID:17283141</ref>  [[http://www.uniprot.org/uniprot/ASPP2_HUMAN ASPP2_HUMAN]] Regulator that plays a central role in regulation of apoptosis and cell growth via its interactions. Regulates TP53 by enhancing the DNA binding and transactivation function of TP53 on the promoters of proapoptotic genes in vivo. Inhibits the ability of APPBP1 to conjugate NEDD8 to CUL1, and thereby decreases APPBP1 ability to induce apoptosis. Impedes cell cycle progression at G2/M. Its apoptosis-stimulating activity is inhibited by its interaction with DDX42.<ref>PMID:11684014</ref> <ref>PMID:12694406</ref> <ref>PMID:19377511</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serine/threonine phosphatases such as PP1 lack substrate specificity and associate with a large array of targeting subunits to achieve the requisite selectivity. The tumour suppressor ASPP (apoptosis-stimulating protein of p53) proteins associate with PP1 catalytic subunits and are implicated in multiple functions from transcriptional regulation to cell junction remodelling. Here we show that Drosophila ASPP is part of a multiprotein PP1 complex and that PP1 association is necessary for several in vivo functions of Drosophila ASPP. We solve the crystal structure of the human ASPP2/PP1 complex and show that ASPP2 recruits PP1 using both its canonical RVxF motif, which binds the PP1 catalytic domain, and its SH3 domain, which engages the PP1 C-terminal tail. The ASPP2 SH3 domain can discriminate between PP1 isoforms using an acidic specificity pocket in the n-Src domain, providing an exquisite mechanism where multiple motifs are used combinatorially to tune binding affinity to PP1.

ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail.,Bertran MT, Mouilleron S, Zhou Y, Bajaj R, Uliana F, Kumar GS, van Drogen A, Lee R, Banerjee JJ, Hauri S, O'Reilly N, Gstaiger M, Page R, Peti W, Tapon N Nat Commun. 2019 Feb 15;10(1):771. doi: 10.1038/s41467-019-08686-0. PMID:30770806<ref>PMID:30770806</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6ghm" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Phosphoprotein phosphatase]]
[[Category: Bertran, T M]]
[[Category: Mouilleron, S]]
[[Category: Tapon, N]]
[[Category: Zhou, Y]]
[[Category: Aspp2]]
[[Category: Hydrolase]]
[[Category: Phosphatase]]
[[Category: Pp1]]