9MIP

CryoEM structure of the Protein Phasphatase 2A (Aalpha-B56gamma-Calpha) holoenzyme complex

9MIP の概要

• エントリーDOI: 10.2210/pdb9mip/pdb
• EMDBエントリー: 48300
• 分子名称: Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha 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)
• 機能のキーワード: pp2a, phosphatase, complex, holoenzyme, heterotrimer, hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 162269.02

構造登録者

Day, A.,Taylor, D. (登録日: 2024-12-13, 公開日: 2025-07-09, 最終更新日: 2025-10-15)

主引用文献

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, 33:1688-1699.e5, 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

実験手法

ELECTRON MICROSCOPY (3.4 Å)