8TTB
Cryo-EM structure of the PP2A:B55-ARPP19 complex
Summary for 8TTB
| Entry DOI | 10.2210/pdb8ttb/pdb |
| EMDB information | 41604 |
| 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 | protein phosphatase 2a:b55 holoenzyme, arpp19 inhibitor, cell cycle regulation, signaling protein, hydrolase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 165589.14 |
| Authors | Fuller, J.R.,Padi, S.K.R.,Peti, W.,Page, R. (deposition date: 2023-08-13, release date: 2023-10-25, Last modification date: 2024-01-17) |
| Primary citation | Padi, S.K.R.,Vos, M.R.,Godek, R.J.,Fuller, J.R.,Kruse, T.,Hein, J.B.,Nilsson, J.,Kelker, M.S.,Page, R.,Peti, W. Cryo-EM structures of PP2A:B55-FAM122A and PP2A:B55-ARPP19. Nature, 625:195-203, 2024 Cited by PubMed Abstract: Progression through the cell cycle is controlled by regulated and abrupt changes in phosphorylation. Mitotic entry is initiated by increased phosphorylation of mitotic proteins, a process driven by kinases, whereas mitotic exit is achieved by counteracting dephosphorylation, a process driven by phosphatases, especially PP2A:B55. Although the role of kinases in mitotic entry is well established, recent data have shown that mitosis is only successfully initiated when the counterbalancing phosphatases are also inhibited. Inhibition of PP2A:B55 is achieved by the intrinsically disordered proteins ARPP19 and FAM122A. Despite their critical roles in mitosis, the mechanisms by which they achieve PP2A:B55 inhibition is unknown. Here, we report the single-particle cryo-electron microscopy structures of PP2A:B55 bound to phosphorylated ARPP19 and FAM122A. Consistent with our complementary NMR spectroscopy studies, both intrinsically disordered proteins bind PP2A:B55, but do so in highly distinct manners, leveraging multiple distinct binding sites on B55. Our extensive structural, biophysical and biochemical data explain how substrates and inhibitors are recruited to PP2A:B55 and provide a molecular roadmap for the development of therapeutic interventions for PP2A:B55-related diseases. PubMed: 38123684DOI: 10.1038/s41586-023-06870-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.77 Å) |
Structure validation
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