2iae: Difference between revisions

Revision as of 18:50, 21 February 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 with and as ligands. Active as Phosphoprotein phosphatase, with EC number 3.1.3.16 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 Thu Feb 21 17:50:47 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 4: / Line 4: @@
 ==Overview==
-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.
+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 Structure==
@@ Line 15: / Line 15: @@
 [[Category: Phosphoprotein phosphatase]]
 [[Category: Protein complex]]
-[[Category: Cho, U.S.]]
+[[Category: Cho, U S.]]
 [[Category: Xu, W.]]
 [[Category: ADD]]
@@ Line 27: / Line 27: @@
 [[Category: tumor suppressor]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:35:24 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:50:47 2008''