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4iyp

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Revision as of 19:32, 4 August 2016

structure of the nPP2Ac-alpha4 complex

Structural highlights

4iyp is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Related:	4i5l, 4i5n
Gene:	alpha4, IBP1, IGBP1 (HUMAN), PP2Ac, ppp2c, PPP2CA (HUMAN)
Activity:	Phosphoprotein phosphatase, with EC number 3.1.3.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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: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.^[1]

Function

[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.^[2] [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'.^[3] ^[4] ^[5]

Publication Abstract from PubMed

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.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Graham JM Jr, Wheeler P, Tackels-Horne D, Lin AE, Hall BD, May M, Short KM, Schwartz CE, Cox TC. A new X-linked syndrome with agenesis of the corpus callosum, mental retardation, coloboma, micrognathia, and a mutation in the Alpha 4 gene at Xq13. Am J Med Genet A. 2003 Nov 15;123A(1):37-44. PMID:14556245 doi:10.1002/ajmg.a.20504
↑ Kong M, Ditsworth D, Lindsten T, Thompson CB. Alpha4 is an essential regulator of PP2A phosphatase activity. Mol Cell. 2009 Oct 9;36(1):51-60. PMID:19818709 doi:S1097-2765(09)00685-6
↑ Hsu W, Zeng L, Costantini F. Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999 Feb 5;274(6):3439-45. PMID:9920888
↑ Abraham D, Podar K, Pacher M, Kubicek M, Welzel N, Hemmings BA, Dilworth SM, Mischak H, Kolch W, Baccarini M. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000 Jul 21;275(29):22300-4. PMID:10801873 doi:10.1074/jbc.M003259200
↑ Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC, Schweiger S, Spiller BW, Wadzinski BE. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit alpha4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012 Jul 13;287(29):24207-15. doi: 10.1074/jbc.M112.368613. Epub, 2012 May 21. PMID:22613722 doi:10.1074/jbc.M112.368613
↑ Jiang L, Stanevich V, Satyshur KA, Kong M, Watkins GR, Wadzinski BE, Sengupta R, Xing Y. Structural basis of protein phosphatase 2A stable latency. Nat Commun. 2013;4:1699. doi: 10.1038/ncomms2663. PMID:23591866 doi:10.1038/ncomms2663

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4iyp"

@@ Line 1: / Line 1: @@
 ==structure of the nPP2Ac-alpha4 complex==
 <StructureSection load='4iyp' size='340' side='right' caption='[[4iyp]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[4iyp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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>
 </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>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i5l|4i5l]], [[4i5n|4i5n]]</td></tr>
-<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>
+<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 HUMAN]), PP2Ac, ppp2c, PPP2CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=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>
+<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://pdbe.org/4iyp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iyp RCSB], [http://www.ebi.ac.uk/pdbsum/4iyp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iyp ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 21: / Line 22: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4iyp" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 28: / Line 30: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Phosphoprotein phosphatase]]
 [[Category: Jiang, L]]

4iyp

From Proteopedia

Revision as of 19:32, 4 August 2016

structure of the nPP2Ac-alpha4 complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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