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PXD073175-1
PXD073175 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Evaluation of cleavable crosslinking for characterization of proteoform structural differences by top-down mass spectrometry |
| Description | Cleavable crosslinking has traditionally been employed in bottom-up mass spectrometry to elucidate protein structure and protein-protein interactions through identification of peptides bearing characteristic mass adducts. Here, we demonstrate the application of cleavable crosslinking in top-down mass spectrometry to enhance fragmentation efficiency and enable precise localization of crosslink sites. We first validated this approach using cytochrome c, a well-characterized model protein. Subsequently, we extended top-down cleavable crosslinking to transthyretin, a natively homotetrameric protein exhibiting extensive proteoform heterogeneity, to investigate whether proteoform variations induce structural changes detectable by this method. Our results confirm that cleavable crosslinks can be detected and characterized by top-down mass spectrometry, with crosslinker cleavage under collisional activation significantly enhancing fragmentation. Application to transthyretin (intramolecular crosslinks) yielded complex crosslinking patterns that precluded complete identification of crosslinks. However, the crosslinking data provided valuable information on solvent-accessible residues, functioning effectively as a covalent labeling strategy. This work establishes cleavable crosslinking as a viable chemical crosslinking approach for top-down mass spectrometry applications. |
| HostingRepository | jPOST |
| AnnounceDate | 2026-01-17 |
| AnnouncementXML | Submission_2026-01-16_12:11:31.812.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Ian Webb |
| SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Equus caballus; NCBI TaxID: 9796; |
| ModificationList | unknown modification; unknown modification |
| Instrument | instrument; Synapt MS |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-01-16 12:11:28 | ID requested | |
| ⏵ 1 | 2026-01-16 12:11:32 | announced |
Publication List
| Renbarger EA, Webb IK, Evaluation of Cleavable Crosslinking for Characterization of Proteoform Structural Differences by Top-Down Mass Spectrometry. Int J Mass Spectrom, 521():(2026) [pubmed] |
Keyword List
| submitter keyword: crosslinking, top-down proteomics |
Contact List
| Ian K. Webb | |
|---|---|
| lab head | |
| Ian Webb | |
| contact affiliation | IU Indianapolis |
| dataset submitter | |
Full Dataset Link List
| jPOST 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://ftp.jpostdb.org/JPST004334/ |




