2IAE: Crystal Structure of a Protein Phosphatase 2A (Pp2a) Holoenzyme

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.
PDB ID: 2IAEDownload
MMDB ID: 84468
PDB Deposition Date: 2006/9/7
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 2IAE: tetrameric; determined by author
Molecular Components in 2IAE
Label Count Molecule
Proteins (3 molecules)
Serine/threonine-protein Phosphatase 2A 65 KDA Regulatory Subunit a Alpha Isoform(Gene symbol: Ppp2r1a)
Molecule annotation
Serine/threonine-protein Phosphatase 2A 56 KDA Regulatory Subunit Gamma Isoform(Gene symbol: PPP2R5C)
Molecule annotation
Serine/threonine-protein Phosphatase 2A Catalytic Subunit Alpha Isoform(Gene symbol: PPP2CA)
Molecule annotation
Nucleotide(1 molecule)
Molecule annotation
Chemicals (2 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB