PXD051339
PXD051339 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Multi-epitope immunocapture of huntingtin reveals striatum-selective molecular signatures in Huntington's disease mouse models |
| Description | Huntington's disease (HD) is a debilitating progressive neurodegenerative disorder that has profound effects on an individual's cognitive, motor, and behavioral functions. HD is caused by mutation in the huntingtin (HTT) gene that results in CAG repeat expansion and production of an aggregation-prone polyglutamine-containing protein (mHTT). The expression of mHTT causes selective degeneration, mainly in the striatum and cortex brain regions. Yet, the molecular signatures that underlie their selective sensitization remain incompletely characterized. In HD mouse models, we systematically employed immunopurification-mass spectrometry using HTT antibodies targeting non-overlapping epitopes to capture distinct sub-cellular pools of HTT complexes and postulate domain-specific interactions. We also identified mHTT- and tissue-dependent interactions at different disease stages, which were validated using targeted mass spectrometry and computational analysis of HD genetic modifiers. Among the polyQ-dependent, striatum-enriched interactions, we identified interaction with the mediator complex that results in its altered nuclear-cytoplasmic distribution. Integrating IP-MS data with thermal profiling of the mediator complex in HTT deficient cells supports an interaction interface with the mediator tail domain. Broadly, striatum-enriched HTT interactions highlight calcium homeostasis and ion transport at the synapse as sensitizing molecular signatures. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-12-29 |
| AnnouncementXML | Submission_2024-12-29_05:34:37.702.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Todd Greco |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Carbamidomethyl; Oxidation; Acetyl |
| Instrument | Q Exactive HF; timsTOF Ultra |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-04-10 09:45:20 | ID requested | |
| ⏵ 1 | 2024-12-29 05:34:38 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: IP-MS, protein interactions, thermal profiling, DIA, pasef, FragPipe, DIANN |
Contact List
| Ileana M Cristea | |
|---|---|
| contact affiliation | Department of Molecular Biology, Princeton University, USA |
| contact email | icristea@princeton.edu |
| lab head | |
| Todd Greco | |
| contact affiliation | Princeton University |
| contact email | tgreco@princeton.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive.ucsd.edu/v07/MSV000094509/ |
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