{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Renbarger EA"],"funding":["NIGMS NIH HHS"],"pagination":["117570"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12798706"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["521"],"pubmed_abstract":["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 "],"journal":["International journal of mass spectrometry"],"pubmed_title":["Evaluation of Cleavable Crosslinking for Characterization of Proteoform Structural Differences by Top-Down Mass Spectrometry."],"pmcid":["PMC12798706"],"funding_grant_id":["R35 GM151251"],"pubmed_authors":["Renbarger EA","Webb IK"],"additional_accession":[]},"is_claimable":false,"name":"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 ","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Mar","modification":"2026-06-06T17:30:14.57Z","creation":"2026-06-03T03:10:39.253Z"},"accession":"S-EPMC12798706","cross_references":{"pubmed":["41536932"],"doi":["10.1016/j.ijms.2026.117570"]}}