PXD061649 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Wnt signalosome assembly is governed by conformational flexibility of Axin and AP2 clathrin adaptor |
Description | Wnt signal transduction relies on the direct inhibition of GSK3 by phosphorylated PPPSPxS motifs within the cytoplasmic tail of the LRP6 co-receptor. How GSK3 is recruited to LRP6 remains unclear. Here, we use nuclear magnetic resonance spectroscopy to identify the membrane-proximal PPPSPxS motif and its flanking sequences as the primary binding site for both Axin and GSK3, and an intrinsically disordered segment of Axin as its LRP6-interacting region (LIR). Co-immunoprecipitation and CRISPR-engineered mutations in endogenous Axin indicate that its docking at LRP6 is antagonized by a phospho-dependent foldback within LIR and by a PRTxR motif that allows Axin and GSK3 to form a multi-pronged interaction that favors their detachment from LRP6. Crucially, signaling by LRP6 also depends on its binding to AP2 clathrin adaptor. We propose that the Wnt-driven clustering of LRP6 within clathrin-coated locales allows the Axin-GSK complex to dock at adjacent LRP6 molecules, while also exposing it to co-targeted kinases that change its activity in Wnt signal transduction. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-30 |
AnnouncementXML | Submission_2025-04-30_03:22:48.311.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Mariann Bienz |
SpeciesList | scientific name: Xenopus laevis (African clawed frog); NCBI TaxID: 8355; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-03-10 07:18:56 | ID requested | |
⏵ 1 | 2025-04-30 03:22:48 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: GSK3 inhibition |
LRP6 co-receptor |
Axin scaffold protein |
AP2 cargo adaptor |
clathrin-coated structures |
Wnt signalosome |
Contact List
Mariann Bienz |
contact affiliation | MRC Laboratory of Molecular Biology Francis Crick Avenue Cambridge Biomedical Campus CB2 0QH Cambridge UK |
contact email | mb2@mrc-lmb.cam.ac.uk |
lab head | |
Mariann Bienz |
contact affiliation | MRC Laboratory of Molecular Biology |
contact email | mb2@mrc-lmb.cam.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD061649
- Label: PRIDE project
- Name: Wnt signalosome assembly is governed by conformational flexibility of Axin and AP2 clathrin adaptor