9C6B
PP2A:B55-p107 substrate complex
Summary for 9C6B
| Entry DOI | 10.2210/pdb9c6b/pdb |
| EMDB information | 45243 |
| 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, ... (6 entities in total) |
| Functional Keywords | pp2a:b55, p107, substrate complex, hydrolase, hydrolase-substrate complex, hydrolase/substrate |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 161742.10 |
| Authors | Page, R.,Peti, W.,Padi, S.,Godek, R.J. (deposition date: 2024-06-07, release date: 2025-05-21, Last modification date: 2025-08-20) |
| Primary citation | 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., 32:1373-1382, 2025 Cited by 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: 40247147DOI: 10.1038/s41594-025-01535-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.6 Å) |
Structure validation
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