9MF5

CryoEM structure of the Protein Phosphatase 2A (Abeta-B56gamma-Calpha) holoenzyme complex

Summary for 9MF5

• Entry DOI: 10.2210/pdb9mf5/pdb
• EMDB information: 48224
• Descriptor: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform, Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform, Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, ... (4 entities in total)
• Functional Keywords: phosphatase, complex, holoenzyme, heterotrimer, signaling protein, hydrolase
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 163167.90

Authors

Day, A.,Taylor, D. (deposition date: 2024-12-09, release date: 2025-07-09, Last modification date: 2025-08-13)

Primary citation

Day, A.,Huang, W.,Leonard, D.,O'Connor, C.M.,Narla, G.,Taylor, D.J.
Regulatory mechanisms of PP2A complex assembly driven by physicochemical differences in A-subunit isoforms.
Structure, 2025

PubMed Abstract: Protein phosphatase 2A (PP2A) is crucial for regulating cellular pathways, with its holoenzyme assembly affecting enzyme function and substrate selection. The PP2A holoenzyme comprises scaffold A-, regulatory B-, and catalytic C-subunits, each with various isoforms. Here, we examine structural and biochemical characteristics of the A-subunit isoforms (Aα and Aβ) and identify different biophysical properties that may promote distinct PP2A functions. Our molecular dynamics simulations and cryo-EM analyses define structural differences in the isoforms that reside primarily at the N-terminus of the A-subunit where it interfaces with regulatory B-subunits. Kinetic analyses show Aβ has a lower binding affinity in complexes with B56 subunits and exhibits unique aggregative properties as a monomeric protein. These findings suggest that the different physicochemical properties between A-subunit isoforms are key to PP2A holoenzyme assembly and function. We predict that the Aβ serves as a reservoir, ensuring that serine-threonine phosphatase activity is maintained during high regulatory demand.

PubMed: 40712571
DOI: 10.1016/j.str.2025.06.013

Experimental method

ELECTRON MICROSCOPY (3.2 Å)