4iyp

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{{STRUCTURE_4iyp| PDB=4iyp | SCENE= }}
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==structure of the nPP2Ac-alpha4 complex==
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===structure of the nPP2Ac-alpha4 complex===
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<StructureSection load='4iyp' size='340' side='right' caption='[[4iyp]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23591866}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4iyp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IYP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IYP FirstGlance]. <br>
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==Disease==
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</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>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i5l|4i5l]], [[4i5n|4i5n]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">alpha4, IBP1, IGBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PP2Ac, ppp2c, PPP2CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=4iyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iyp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4iyp RCSB], [http://www.ebi.ac.uk/pdbsum/4iyp PDBsum]</span></td></tr>
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</table>
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== Disease ==
[[http://www.uniprot.org/uniprot/IGBP1_HUMAN IGBP1_HUMAN]] Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia. Defects in IGBP1 are the cause of mental retardation syndromic X-linked type 28 (MRXS28) [MIM:[http://omim.org/entry/300472 300472]]; also known as agenesis of the corpus callosum with mental retardation, ocular coloboma and micrognathia. A syndrome that is characterized by coloboma of the iris and optic nerve, severe retrognathia, intellectual deficit, and agenesis of the corpus callosum.<ref>PMID:14556245</ref>
[[http://www.uniprot.org/uniprot/IGBP1_HUMAN IGBP1_HUMAN]] Agenesis of the corpus callosum - intellectual deficit - coloboma - micrognathia. Defects in IGBP1 are the cause of mental retardation syndromic X-linked type 28 (MRXS28) [MIM:[http://omim.org/entry/300472 300472]]; also known as agenesis of the corpus callosum with mental retardation, ocular coloboma and micrognathia. A syndrome that is characterized by coloboma of the iris and optic nerve, severe retrognathia, intellectual deficit, and agenesis of the corpus callosum.<ref>PMID:14556245</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/IGBP1_HUMAN IGBP1_HUMAN]] Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of PP2A, PP4 and PP6 phosphatases catalytic subunits by protecting them from degradative polyubiquitination until they associate with regulatory subunits.<ref>PMID:19818709</ref> [[http://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The catalytic subunit of protein phosphatase 2A (PP2Ac) is stabilized in a latent form by alpha4, a regulatory protein essential for cell survival and biogenesis of all PP2A complexes. Here we report the structure of alpha4 bound to the N-terminal fragment of PP2Ac. This structure suggests that alpha4 binding to the full-length PP2Ac requires local unfolding near the active site, which perturbs the scaffold subunit binding site at the opposite surface via allosteric relay. These changes stabilize an inactive conformation of PP2Ac and convert oligomeric PP2A complexes to the alpha4 complex upon perturbation of the active site. The PP2Ac-alpha4 interface is essential for cell survival and sterically hinders a PP2A ubiquitination site, important for the stability of cellular PP2Ac. Our results show that alpha4 is a scavenger chaperone that binds to and stabilizes partially folded PP2Ac for stable latency, and reveal a mechanism by which alpha4 regulates cell survival, and biogenesis and surveillance of PP2A holoenzymes.
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==Function==
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Structural basis of protein phosphatase 2A stable latency.,Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y Nat Commun. 2013;4:1699. doi: 10.1038/ncomms2663. PMID:23591866<ref>PMID:23591866</ref>
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[[http://www.uniprot.org/uniprot/IGBP1_HUMAN IGBP1_HUMAN]] Associated to surface IgM-receptor; may be involved in signal transduction. Involved in regulation of the catalytic activity of PP2A, PP4 and PP6 phosphatases catalytic subunits by protecting them from degradative polyubiquitination until they associate with regulatory subunits.<ref>PMID:19818709</ref> [[http://www.uniprot.org/uniprot/PP2AA_HUMAN PP2AA_HUMAN]] PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGOL2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.<ref>PMID:9920888</ref> <ref>PMID:10801873</ref> <ref>PMID:22613722</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4iyp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IYP OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:023591866</ref><references group="xtra"/><references/>
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*[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Phosphoprotein phosphatase]]
[[Category: Phosphoprotein phosphatase]]
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[[Category: Jiang, L.]]
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[[Category: Jiang, L]]
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[[Category: Satyshur, K A.]]
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[[Category: Satyshur, K A]]
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[[Category: Stanevich, V.]]
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[[Category: Stanevich, V]]
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[[Category: Xing, Y.]]
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[[Category: Xing, Y]]
[[Category: Alpha4]]
[[Category: Alpha4]]
[[Category: Helix motif]]
[[Category: Helix motif]]

Revision as of 12:42, 21 December 2014

structure of the nPP2Ac-alpha4 complex

4iyp, resolution 2.80Å

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