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PXD052957

PXD052957 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAggregate-selective removal of pathological tau via clustering-activated degraders
DescriptionHomotypic protein assembly is a critical mediator of biological function and disease state. Selective degradation of protein assemblies, while sparing monomeric forms, is required for interrogation of biological mechanisms and assembly-specific therapeutic intervention. We have exploited the requirement of intermolecular clustering for activation of the E3 ligase TRIM21 to produce TRIM21-nanobody fusions capable of rapidly and selectively degrading assembled proteins. We demonstrate this approach against histone 2B-GFP and tau, a protein that undergoes pathological aggregation in Alzheimer’s and other neurodegenerative diseases. Intracellular expression of TRIM21-nanobody degraders prevented or reversed tau aggregation in culture systems and in vivo, with minimal impact on soluble tau. Our results demonstrate that homotypic quaternary structure is a property of proteins that may be exploited for their selective degradation.
HostingRepositoryPRIDE
AnnounceDate2025-05-07
AnnouncementXMLSubmission_2025-05-06_18:39:44.800.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCatarina Franco
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-06-10 03:38:34ID requested
12025-05-06 18:39:45announced
Publication List
10.1126/science.adp5186;
Benn J, Cheng S, Keeling S, Smith AE, Vaysburd MJ, B, ö, ken D, Miller LVC, Katsinelos T, Franco C, Dupr, é E, Danis C, Landrieu I, Bu, é, e L, Klenerman D, James LC, McEwan WA, Aggregate-selective removal of pathological tau by clustering-activated degraders. Science, 385(6712):1009-1016(2024) [pubmed]
Keyword List
submitter keyword: neurodegenerative diseases, TRIM21, tau
Contact List
Leo C James
contact affiliationMRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
contact emaillcj@mrc-lmb.cam.ac.uk
lab head
Catarina Franco
contact affiliationMRC Laboratory of Molecular Biology
contact emailcffranco@mrc-lmb.cam.ac.uk
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
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