7SOY
The structure of the PP2A-B56gamma1 holoenzyme-PME-1 complex
Summary for 7SOY
| Entry DOI | 10.2210/pdb7soy/pdb |
| EMDB information | 25363 |
| Descriptor | Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform, Isoform Gamma-1 of 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 | the structure of pp2a-b56gamma holoenzyme-pme-1 complex, recombination |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 196062.15 |
| Authors | Li, Y.,Balakrishnan, V.K.,Rowse, M.,Novikova, I.V.,Xing, Y. (deposition date: 2021-11-01, release date: 2022-08-31, Last modification date: 2024-06-05) |
| Primary citation | Li, Y.,Balakrishnan, V.K.,Rowse, M.,Wu, C.G.,Bravos, A.P.,Yadav, V.K.,Ivarsson, Y.,Strack, S.,Novikova, I.V.,Xing, Y. Coupling to short linear motifs creates versatile PME-1 activities in PP2A holoenzyme demethylation and inhibition. Elife, 11:-, 2022 Cited by PubMed Abstract: Protein phosphatase 2A (PP2A) holoenzymes target broad substrates by recognizing short motifs via regulatory subunits. PP2A methylesterase 1 (PME-1) is a cancer-promoting enzyme and undergoes methylesterase activation upon binding to the PP2A core enzyme. Here, we showed that PME-1 readily demethylates different families of PP2A holoenzymes and blocks substrate recognition in vitro. The high-resolution cryoelectron microscopy structure of a PP2A-B56 holoenzyme-PME-1 complex reveals that PME-1 disordered regions, including a substrate-mimicking motif, tether to the B56 regulatory subunit at remote sites. They occupy the holoenzyme substrate-binding groove and allow large structural shifts in both holoenzyme and PME-1 to enable multipartite contacts at structured cores to activate the methylesterase. B56 interface mutations selectively block PME-1 activity toward PP2A-B56 holoenzymes and affect the methylation of a fraction of total cellular PP2A. The B56 interface mutations allow us to uncover B56-specific PME-1 functions in p53 signaling. Our studies reveal multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile PME-1 activities derived from coupling substrate-mimicking motifs to dynamic structured cores. PubMed: 35924897DOI: 10.7554/eLife.79736 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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