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| | ==structure of the nPP2Ac-alpha4 complex== | | ==structure of the nPP2Ac-alpha4 complex== |
| - | <StructureSection load='4iyp' size='340' side='right' caption='[[4iyp]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4iyp' size='340' side='right'caption='[[4iyp]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == 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 [https://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 [https://proteopedia.org/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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.797Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4iyp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iyp OCA], [https://pdbe.org/4iyp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iyp RCSB], [https://www.ebi.ac.uk/pdbsum/4iyp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iyp ProSAT]</span></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>
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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> | + | |
| | </table> | | </table> |
| | == Disease == | | == 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> | + | [https://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:[https://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> |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | 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 4iyp" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Serine/threonine protein phosphatase|Serine/threonine protein phosphatase]] | + | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Large Structures]] |
| - | [[Category: Jiang, L]] | + | [[Category: Jiang L]] |
| - | [[Category: Satyshur, K A]] | + | [[Category: Satyshur KA]] |
| - | [[Category: Stanevich, V]] | + | [[Category: Stanevich V]] |
| - | [[Category: Xing, Y]] | + | [[Category: Xing Y]] |
| - | [[Category: Alpha4]]
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| - | [[Category: Helix motif]]
| + | |
| - | [[Category: Latency]]
| + | |
| - | [[Category: Pp2a]]
| + | |
| - | [[Category: Signaling protein]]
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| Structural highlights
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]
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ 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
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