2iae: Difference between revisions

Revision as of 07:15, 4 May 2008

Crystal structure of a protein phosphatase 2A (PP2A) holoenzyme.

OverviewOverview

Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer's disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB'C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B' subunits together on the same side. The regulatory B' subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B' subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B' subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.

About this StructureAbout this Structure

2IAE is a Protein complex structure of sequences from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme., Cho US, Xu W, Nature. 2007 Jan 4;445(7123):53-7. Epub 2006 Nov 1. PMID:17086192 Page seeded by OCA on Sun May 4 07:15:33 2008

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OCA

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 [[Image:2iae.jpg|left|200px]]
- {{Structure
+<!--
-|PDB= 2iae |SIZE=350|CAPTION= <scene name='initialview01'>2iae</scene>, resolution 3.50&Aring;
+The line below this paragraph, containing "STRUCTURE_2iae", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ACB:3-METHYL-ASPARTIC+ACID'>ACB</scene>, <scene name='pdbligand=ADD:2,6,8-TRIMETHYL-3-AMINO-9-BENZYL-9-METHOXYNONANOIC+ACID'>ADD</scene>, <scene name='pdbligand=CAB:4-CARBOXY-4-AMINOBUTANAL'>CAB</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MAA:N-METHYLALANINE'>MAA</scene>, <scene name='pdbligand=MLL:METHYL+L-LEUCINATE'>MLL</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <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>
+or leave the SCENE parameter empty for the default display.
-|GENE= Ppp2r1a ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), PPP2R5C, KIAA0044 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PPP2CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_2iae|  PDB=2iae  |  SCENE=  }}
-|RELATEDENTRY=[[1b3u|1B3U]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2iae FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2iae OCA], [http://www.ebi.ac.uk/pdbsum/2iae PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2iae RCSB]</span>
-}}
 '''Crystal structure of a protein phosphatase 2A (PP2A) holoenzyme.'''
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 [[Category: Cho, U S.]]
 [[Category: Xu, W.]]
-[[Category: b56]]
+[[Category: B56]]
-[[Category: crystal structure]]
+[[Category: Crystal structure]]
-[[Category: methylation]]
+[[Category: Methylation]]
-[[Category: phosphatase]]
+[[Category: Phosphatase]]
-[[Category: pp2a]]
+[[Category: Pp2a]]
-[[Category: protein phosphorylation]]
+[[Category: Protein phosphorylation]]
-[[Category: tumor suppressor]]
+[[Category: Tumor suppressor]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 07:15:33 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:41:37 2008''