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PXD039200

PXD039200 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn affinity-directed phosphatase (AdPhosphatase) system for targeted protein dephosphorylation
DescriptionReversible protein phosphorylation, catalysed by protein kinases and phosphatases, is a fundamental process that controls protein function and intracellular signalling. Failure of phospho-control accounts for many human diseases. While a kinase phosphorylates multiple substrates, a substrate is often phosphorylated by multiple kinases. This renders phospho control at the substrate level challenging, as it requires inhibition of multiple kinases, which would thus affect other kinase substrates. Here, we describe the development and application of the affinity-directed phosphatase (AdPhosphatase) system for targeted dephosphorylation of specific phospho-substrates. By deploying the Protein Phosphatase 1 or 2A catalytic subunits conjugated to an antigen-stabilised anti-GFP nanobody, we can promote the dephosphorylation of two independent phospho-proteins, FAM83D or ULK1, knocked in with GFP-tags using CRISPR/Cas9, with exquisite specificity. By redirecting protein phosphatases to neo-substrates through nanobody-mediated proximity, AdPhosphatase can alter the phospho-status and function of target proteins and thus, offers a new modality for potential drug discovery approaches.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:29:16.117.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGopal Sapkota
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-01-02 19:20:12ID requested
12023-02-01 07:16:38announced
22023-11-14 08:29:17announced2023-11-14: Updated project metadata.
Publication List
Simpson LM, Fulcher LJ, Sathe G, Brewer A, Zhao JF, Squair DR, Crooks J, Wightman M, Wood NT, Gourlay R, Varghese J, Soares RF, Sapkota GP, An affinity-directed phosphatase, AdPhosphatase, system for targeted protein dephosphorylation. Cell Chem Biol, 30(2):188-202.e6(2023) [pubmed]
Keyword List
submitter keyword: Affinity-directed phosphatase
AdPhosphatase
Targeted dephosphorylation
PPP1CA;PPP2CA
Nanobody
ULK1
FAM83D
Contact List
Professor Gopal Sapkota
contact affiliationProfessor Gopal Sapkota MRC Investigator MRC Protein Phosphorylation & Ubiquitylation Unit Sir James Black Centre School of Life Sciences University of Dundee Dundee DD1 5EH
 United Kingdom


contact emailg.sapkota@dundee.ac.uk
lab head
Gopal Sapkota
contact affiliationUniversity of Dundee
contact emailg.sapkota@dundee.ac.uk
dataset submitter
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Dataset FTP location
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