9C6B

PP2A:B55-p107 substrate complex

9C6B の概要

• エントリーDOI: 10.2210/pdb9c6b/pdb
• EMDBエントリー: 45243
• 分子名称: 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, ... (6 entities in total)
• 機能のキーワード: pp2a:b55, p107, substrate complex, hydrolase, hydrolase-substrate complex, hydrolase/substrate
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 161742.10

構造登録者

Page, R.,Peti, W.,Padi, S.,Godek, R.J. (登録日: 2024-06-07, 公開日: 2025-05-21)

主引用文献

Padi, S.K.R.,Godek, R.J.,Peti, W.,Page, R.
Cryo-EM structures of PP2A:B55 with p107 and Eya3 define substrate recruitment.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: Phosphoprotein phosphatases (PPPs) achieve specificity by binding substrates and regulators using PPP-specific short motifs. Protein phosphatase 2A (PP2A) is a highly conserved phosphatase that regulates cell signaling and is a tumor suppressor. Here, we use cryo-electron microscopy and nuclear magnetic resonance (NMR) spectroscopy to investigate the mechanisms of human p107 substrate and Eya3 regulator recruitment to the PP2A:B55 holoenzyme. We show that, while they associate with B55 using a common set of interaction pockets, the mechanism of substrate and regulator binding differs and is distinct from that observed for PP2A:B56 and other PPPs. We also identify the core B55 recruitment motif in Eya3 proteins, a sequence conserved amongst the Eya family. Lastly, using NMR-based dephosphorylation assays, we demonstrate how B55 recruitment directs PP2A:B55 fidelity through the selective dephosphorylation of specific phosphosites. As PP2A:B55 orchestrates mitosis and DNA damage repair, these data provide a roadmap for pursuing new avenues to therapeutically target this complex by individually blocking a subset of regulators that use different B55 interaction sites.

PubMed: 40247147
DOI: 10.1038/s41594-025-01535-3

実験手法

ELECTRON MICROSCOPY (2.6 Å)