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3p71

From Proteopedia

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Crystal structure of the complex of LCMT-1 and PP2A

Structural highlights

3p71 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.7Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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'.^[1] ^[2] ^[3]

Publication Abstract from PubMed

Proper formation of protein phosphatase 2A (PP2A) holoenzymes is essential for the fitness of all eukaryotic cells. Carboxyl methylation of the PP2A catalytic subunit plays a critical role in regulating holoenzyme assembly; methylation is catalyzed by PP2A-specific methyltransferase LCMT-1, an enzyme required for cell survival. We determined crystal structures of human LCMT-1 in isolation and in complex with PP2A stabilized by a cofactor mimic. The structures show that the LCMT-1 active-site pocket recognizes the carboxyl terminus of PP2A, and, interestingly, the PP2A active site makes extensive contacts to LCMT-1. We demonstrated that activation of the PP2A active site stimulates methylation, suggesting a mechanism for efficient conversion of activated PP2A into substrate-specific holoenzymes, thus minimizing unregulated phosphatase activity or formation of inactive holoenzymes. A dominant-negative LCMT-1 mutant attenuates the cell cycle without causing cell death, likely by inhibiting uncontrolled phosphatase activity. Our studies suggested mechanisms of LCMT-1 in tight control of PP2A function, important for the cell cycle and cell survival.

The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1.,Stanevich V, Jiang L, Satyshur KA, Li Y, Jeffrey PD, Li Z, Menden P, Semmelhack MF, Xing Y Mol Cell. 2011 Feb 4;41(3):331-42. PMID:21292165^[4]

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

References

↑ 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
↑ Stanevich V, Jiang L, Satyshur KA, Li Y, Jeffrey PD, Li Z, Menden P, Semmelhack MF, Xing Y. The Structural Basis for Tight Control of PP2A Methylation and Function by LCMT-1. Mol Cell. 2011 Feb 4;41(3):331-42. PMID:21292165 doi:10.1016/j.molcel.2010.12.030

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3p71"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the complex of LCMT-1 and PP2A==
-<StructureSection load='3p71' size='340' side='right' caption='[[3p71]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='3p71' size='340' side='right'caption='[[3p71]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3p71]] 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=3P71 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3P71 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3p71]] 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=3P71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3P71 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AN6:5-{[(3S)-3-AMINO-3-CARBOXYPROPYL](ETHYL)AMINO}-5-DEOXYADENOSINE'>AN6</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.7&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iei|3iei]], [[2ie3|2ie3]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AN6:5-{[(3S)-3-AMINO-3-CARBOXYPROPYL](ETHYL)AMINO}-5-DEOXYADENOSINE'>AN6</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CGI-68, LCMT, LCMT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PPP2CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3p71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p71 OCA], [https://pdbe.org/3p71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3p71 RCSB], [https://www.ebi.ac.uk/pdbsum/3p71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3p71 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>
-<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=3p71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3p71 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3p71 RCSB], [http://www.ebi.ac.uk/pdbsum/3p71 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[https://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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3p71" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[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: Leucine carboxymethyltransferase-1]]
-[[Category: Methyltransferase]]
-[[Category: S-adenosyl-l-methionine]]
-[[Category: Serine/threonine protein keywds 2 phosphatase 2a]]
-[[Category: Transferase-hydrolase complex]]

3p71

From Proteopedia

Current revision

Crystal structure of the complex of LCMT-1 and PP2A

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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