PXD039200 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | An affinity-directed phosphatase (AdPhosphatase) system for targeted protein dephosphorylation |
Description | Reversible 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. |
HostingRepository | PRIDE |
AnnounceDate | 2023-11-14 |
AnnouncementXML | Submission_2023-11-14_08:29:16.117.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Gopal Sapkota |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-01-02 19:20:12 | ID requested | |
1 | 2023-02-01 07:16:38 | announced | |
⏵ 2 | 2023-11-14 08:29:17 | announced | 2023-11-14: 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 affiliation | Professor 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 email | g.sapkota@dundee.ac.uk |
lab head | |
Gopal Sapkota |
contact affiliation | University of Dundee |
contact email | g.sapkota@dundee.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD039200
- Label: PRIDE project
- Name: An affinity-directed phosphatase (AdPhosphatase) system for targeted protein dephosphorylation