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PXD073175-1

PXD073175 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEvaluation of cleavable crosslinking for characterization of proteoform structural differences by top-down mass spectrometry
DescriptionCleavable 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.
HostingRepositoryjPOST
AnnounceDate2026-01-17
AnnouncementXMLSubmission_2026-01-16_12:11:31.812.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterIan Webb
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606; scientific name: Equus caballus; NCBI TaxID: 9796;
ModificationListunknown modification; unknown modification
Instrumentinstrument; Synapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-16 12:11:28ID requested
12026-01-16 12:11:32announced
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 affiliationIU Indianapolis
dataset submitter
Full Dataset Link List
jPOST dataset URI
Dataset FTP location
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