PXD038956-1
PXD038956 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Tracking chromatin state changes using nanoscale photo proximity labeling |
| Description | Interactions between biomolecules underlie all cellular processes, and ultimately control cell fate. Perturbation of native interactions through mutation, changes in expression levels, or external stimuli leads to altered cellular physiology and can result in either disease or therapeutic effects. Mapping these interactions and determining how they respond to stimulus is the genesis of many drug development efforts, leading to new therapeutic targets and improvements in human health. However, in the complex environment of the nucleus it is challenging to determine protein-protein interactions due to low abundance, transient or multi-valent binding, and a lack of technologies that are able to interrogate these interactions without disrupting the protein binding surface under study. Here, we describe a method for the traceless incorporation of Ir-photosensitizers into the nuclear microenvironment using engineered split inteins. These Ir-catalysts can activate diazirine warheads via Dexter energy transfer to form reactive carbenes within a ~10 nm radius, cross-linking with proteins within the immediate microenvironment (a process termed uMap) for analysis via quantitative chemoproteomics. Additionally, we show that this nanoscale proximity labeling method can reveal the critical changes in interactomes in the presence of cancer-associated mutations, as well as treatment with small-molecule inhibitors. uMap improves our fundamental understanding of nuclear protein-protein interactions, and in doing so is expected to have a significant impact on the field of epigenetic drug discovery in both academia and industry. |
| HostingRepository | MassIVE |
| AnnounceDate | 2022-12-20 |
| AnnouncementXML | Submission_2022-12-20_07:47:15.691.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Ciaran Seath |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Pyro-carbamidomethyl |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2022-12-19 14:44:02 | ID requested | |
| ⏵ 1 | 2022-12-20 07:47:16 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Chromatin, Proximity labeling, Target Identification |
Contact List
| Tom Muir | |
|---|---|
| contact affiliation | Princeton |
| contact email | Muir@princeton.edu |
| lab head | |
| David MacMillan | |
| contact affiliation | Princeton |
| contact email | dmacmill@princeton.edu |
| lab head | |
| Ciaran Seath | |
| contact affiliation | UF-Scripps |
| contact email | cseath@ufl.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/MSV000090929/ |
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