View source for 2pkg


==Structure of a complex between the A subunit of protein phosphatase 2A and the small t antigen of SV40==
<StructureSection load='2pkg' size='340' side='right'caption='[[2pkg]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2pkg]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/ ] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PKG FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP2R1A ([https://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=2pkg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pkg OCA], [https://pdbe.org/2pkg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pkg RCSB], [https://www.ebi.ac.uk/pdbsum/2pkg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pkg ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/2AAA_HUMAN 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.<ref>PMID:16580887</ref>  [[https://www.uniprot.org/uniprot/ST_SV40 ST_SV40]] Promotes efficient viral genome replication by accelerating both G1 and S phase progression of the cell cycle. Inhibits host PP2A by binding to the A subunit, thereby displacing lower affinity regulatory B subunit. Inactivation of PP2A in turn results in the transactivation of cyclin A and cyclin D1 promoters. Late during the infection cycle, ST may induce dephosphorylation of host eIF4E-binding protein EIF4EBP1 leading to the inhibition of cap-dependent translation. May establish and maintain high levels of viral genomes during persistent infection in cell culture.<ref>PMID:15680424</ref> <ref>PMID:15890927</ref> <ref>PMID:17936323</ref> <ref>PMID:8794333</ref> <ref>PMID:8917510</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pk/2pkg_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2pkg ConSurf].
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== Publication Abstract from PubMed ==
The small t antigen (ST) of DNA tumor virus SV40 facilitates cellular transformation by disrupting the functions of protein phosphatase 2A (PP2A) through a poorly defined mechanism. The crystal structure of the core domain of SV40 ST bound to the scaffolding subunit of human PP2A reveals that the ST core domain has a novel zinc-binding fold and interacts with the conserved ridge of HEAT repeats 3-6, which overlaps with the binding site for the B' (also called PR61 or B56) regulatory subunit. ST has a lower binding affinity than B' for the PP2A core enzyme. Consequently, ST does not efficiently displace B' from PP2A holoenzymes in vitro. Notably, ST inhibits PP2A phosphatase activity through its N-terminal J domain. These findings suggest that ST may function mainly by inhibiting the phosphatase activity of the PP2A core enzyme, and to a lesser extent by modulating assembly of the PP2A holoenzymes.

Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40.,Chen Y, Xu Y, Bao Q, Xing Y, Li Z, Lin Z, Stock JB, Jeffrey PD, Shi Y Nat Struct Mol Biol. 2007 Jun;14(6):527-34. Epub 2007 May 27. PMID:17529992<ref>PMID:17529992</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2pkg" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Jeffrey, P D]]
[[Category: Shi, Y]]
[[Category: Hydrolase regulator-viral protein complex]]
[[Category: Protein phosphatase 2a]]
[[Category: Regulation]]
[[Category: Small t antigen]]
[[Category: Sv40]]