PXD049307-1
PXD049307 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Substrate recognition principles for PP2A-B55 |
| Description | The trimeric PP2A-B55 phosphoprotein phosphatase regulates a plethora of fundamental signaling pathways throughout eukaryotes. How PP2A-B55 selects its substrates presents a severe knowledge gap in our understanding of phospho-dependent signaling. By integrating AlphaFold modelling with comprehensive experimental high-resolution mutational scanning, we show that alpha-helices in interactors bind a conserved platform on the B55 regulatory subunit. Despite limited sequence similarity, these alpha-helices share key amino acid determinants that engage hydrophobic and electrostatic patches on B55 in a remarkably similar way. We characterize a total of 15 instances in yeast, humans, and viruses, suggesting an evolutionarily conserved mechanism. Using this insight and deep learning protein design, we generate a specific and highly potent competitive peptide inhibitor that binds to B55 with low nanomolar affinity. With this inhibitor, we uncover that PP2A-B55 regulates the nuclear exosome targeting (NEXT) complex by binding to an alpha-helical recruitment module in one of its core components, RBM7. Collectively, our findings provide a framework for the understanding and interrogation of PP2A-B55 in health and disease. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-08-22 |
| AnnouncementXML | Submission_2024-08-22_10:32:34.194.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Mark Adamo |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Carbamidomethyl; Phospho; GG |
| Instrument | Orbitrap Fusion; Orbitrap Fusion Lumos; Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-02-09 12:17:56 | ID requested | |
| ⏵ 1 | 2024-08-22 10:32:34 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: PP2A-B55, B55, alpha-helix, NEXT, RBM7 |
Contact List
| Arminja Kettenbach | |
|---|---|
| contact affiliation | The Geisel School of Medicine at Dartmouth |
| contact email | arminja.n.kettenbach@dartmouth.edu |
| lab head | |
| Mark Adamo | |
| contact affiliation | Dartmouth College |
| contact email | mark.e.adamo@dartmouth.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/v07/MSV000094053/ |
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