3DW8

Structure of a Protein Phosphatase 2A Holoenzyme with B55 subunit

Summary for 3DW8

• Entry DOI: 10.2210/pdb3dw8/pdb
• Related PRD ID: PRD_000212
• Descriptor: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, ... (5 entities in total)
• Functional Keywords: holoenzyme, b55, pr55, wd repeat, hydrolase, iron, manganese, metal-binding, methylation, phosphoprotein, protein phosphatase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens; More
• Cellular location: Cytoplasm (By similarity): P30153; Cytoplasm: P67775
• Total number of polymer chains: 8
• Total formula weight: 306541.98

Authors

Xu, Y.,Chen, Y.,Zhang, P.,Jeffrey, P.D.,Shi, Y. (deposition date: 2008-07-21, release date: 2008-10-07, Last modification date: 2024-04-03)

Primary citation

Xu, Y.,Chen, Y.,Zhang, P.,Jeffrey, P.D.,Shi, Y.
Structure of a protein phosphatase 2A holoenzyme: insights into B55-mediated Tau dephosphorylation.
Mol.Cell, 31:873-885, 2008

PubMed Abstract: Protein phosphatase 2A (PP2A) regulates many essential aspects of cellular physiology. Members of the regulatory B/B55/PR55 family are thought to play a key role in the dephosphorylation of Tau, whose hyperphosphorylation contributes to Alzheimer's disease. The underlying mechanisms of the PP2A-Tau connection remain largely enigmatic. Here, we report the complete reconstitution of a Tau dephosphorylation assay and the crystal structure of a heterotrimeric PP2A holoenzyme involving the regulatory subunit Balpha. We show that Balpha specifically and markedly facilitates dephosphorylation of the phosphorylated Tau in our reconstituted assay. The Balpha subunit comprises a seven-bladed beta propeller, with an acidic, substrate-binding groove located in the center of the propeller. The beta propeller latches onto the ridge of the PP2A scaffold subunit with the help of a protruding beta hairpin arm. Structure-guided mutagenesis studies revealed the underpinnings of PP2A-mediated dephosphorylation of Tau.

PubMed: 18922469
DOI: 10.1016/j.molcel.2008.08.006

Experimental method

X-RAY DIFFRACTION (2.85 Å)