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PXD049307

PXD049307 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSubstrate recognition principles for PP2A-B55
DescriptionThe 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.
HostingRepositoryMassIVE
AnnounceDate2024-08-22
AnnouncementXMLSubmission_2024-08-22_10:32:34.194.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterMark Adamo
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListOxidation; Carbamidomethyl; Phospho; GG
InstrumentOrbitrap Fusion; Orbitrap Fusion Lumos; Q Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-02-09 12:17:56ID requested
12024-08-22 10:32:34announced
Publication List
no publication
Keyword List
submitter keyword: PP2A-B55, B55, alpha-helix, NEXT, RBM7
Contact List
Arminja Kettenbach
contact affiliationThe Geisel School of Medicine at Dartmouth
contact emailarminja.n.kettenbach@dartmouth.edu
lab head
Mark Adamo
contact affiliationDartmouth College
contact emailmark.e.adamo@dartmouth.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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