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3c5w

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Revision as of 07:16, 21 August 2019

Complex between PP2A-specific methylesterase PME-1 and PP2A core enzyme

Structural highlights

3c5w is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3c5v
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[2AAA_HUMAN] The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.^[1] [PPME1_HUMAN] Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.^[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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Protein phosphatase 2A (PP2A) is an important serine/threonine phosphatase that plays a role in many biological processes. Reversible carboxyl methylation of the PP2A catalytic subunit is an essential regulatory mechanism for its function. Demethylation and negative regulation of PP2A is mediated by a PP2A-specific methylesterase PME-1, which is conserved from yeast to humans. However, the underlying mechanism of PME-1 function remains enigmatic. Here we report the crystal structures of PME-1 by itself and in complex with a PP2A heterodimeric core enzyme. The structures reveal that PME-1 directly binds to the active site of PP2A and that this interaction results in the activation of PME-1 by rearranging the catalytic triad into an active conformation. Strikingly, these interactions also lead to inactivation of PP2A by evicting the manganese ions that are required for the phosphatase activity of PP2A. These observations identify a dual role of PME-1 that regulates PP2A activation, methylation, and holoenzyme assembly in cells.

Structural mechanism of demethylation and inactivation of protein phosphatase 2A.,Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y Cell. 2008 Apr 4;133(1):154-63. PMID:18394995^[6]

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

References

↑ Tang Z, Shu H, Qi W, Mahmood NA, Mumby MC, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006 May;10(5):575-85. Epub 2006 Mar 30. PMID:16580887 doi:10.1016/j.devcel.2006.03.010
↑ Ogris E, Du X, Nelson KC, Mak EK, Yu XX, Lane WS, Pallas DC. A protein phosphatase methylesterase (PME-1) is one of several novel proteins stably associating with two inactive mutants of protein phosphatase 2A. J Biol Chem. 1999 May 14;274(20):14382-91. PMID:10318862
↑ 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
↑ Xing Y, Li Z, Chen Y, Stock JB, Jeffrey PD, Shi Y. Structural mechanism of demethylation and inactivation of protein phosphatase 2A. Cell. 2008 Apr 4;133(1):154-63. PMID:18394995 doi:http://dx.doi.org/10.1016/j.cell.2008.02.041

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/3c5w"

@@ Line 1: / Line 1: @@
 ==Complex between PP2A-specific methylesterase PME-1 and PP2A core enzyme==
-<StructureSection load='3c5w' size='340' side='right' caption='[[3c5w]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='3c5w' size='340' side='right'caption='[[3c5w]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[3c5w]] is a 3 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=3C5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3C5W FirstGlance]. <br>
@@ Line 13: / Line 13: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c5/3c5w_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c5/3c5w_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 28: / Line 28: @@
 </div>
 <div class="pdbe-citations 3c5w" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Methylesterase|Methylesterase]]
+*[[Protein phosphatase|Protein phosphatase]]
 == References ==
 <references/>
@@ Line 33: / Line 37: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Chen, Y]]
 [[Category: Jeffrey, P D]]

3c5w

From Proteopedia

Revision as of 07:16, 21 August 2019

Complex between PP2A-specific methylesterase PME-1 and PP2A core enzyme

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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