PXD052957-1

PXD052957 is an original dataset announced via ProteomeXchange.

Title	Aggregate-selective removal of pathological tau via clustering-activated degraders
Description	Homotypic 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-06_18:39:44.800.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Catarina Franco
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-10 03:38:34	ID requested
⏵ 1	2025-05-06 18:39:45	announced

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]

submitter keyword: neurodegenerative diseases, TRIM21, tau

Leo C James
contact affiliation	MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
contact email	lcj@mrc-lmb.cam.ac.uk
lab head
Catarina Franco
contact affiliation	MRC Laboratory of Molecular Biology
contact email	cffranco@mrc-lmb.cam.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD052957

PRIDE project URI

• PRIDE
  1. PXD052957
     1. Label: PRIDE project
     2. Name: Aggregate-selective removal of pathological tau via clustering-activated degraders