{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu FC"],"funding":["Division of Chemistry","Office of Postdoctoral Affairs, Florida State University","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["4459-4467"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7339587"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["92(6)"],"pubmed_abstract":["Glycoproteins play a central role in many biological processes including disease mechanisms. Nevertheless, because glycoproteins are heterogeneous entities, it remains unclear how glycosylation modulates the protein structure and function. Here, we assess the ability of tandem-trapped ion mobility spectrometry-mass spectrometry (tandem-TIMS/MS) to characterize the structure and sequence of the homotetrameric glycoprotein avidin. We show that (1) tandem-TIMS/MS retains native-like avidin tetramers with deeply buried solvent particles; (2) applying high activation voltages in the interface of tandem-TIMS results in collision-induced dissociation (CID) of avidin tetramers into compact monomers, dimers, and trimers with cross sections consistent with X-ray structures and reports from surface-induced dissociation (SID); (3) avidin oligomers are best described as heterogeneous ensembles with (essentially) random combinations of monomer glycoforms; (4) native top-down sequence analysis of the avidin tetramer is possible by CID in tandem-TIMS. Overall, our results demonstrate that tandem-TIMS/MS has the potential to correlate individual proteoforms to variations in protein structure."],"journal":["Analytical chemistry"],"pubmed_title":["Structural Analysis of the Glycoprotein Complex Avidin by Tandem-Trapped Ion Mobility Spectrometry-Mass Spectrometry (Tandem-TIMS/MS)."],"pmcid":["PMC7339587"],"funding_grant_id":["R01 GM135682","CHE-1654608","R01GM135682"],"pubmed_authors":["Bleiholder C","Liu FC","Park MA","Ridgeway ME","Cropley TC"],"additional_accession":[]},"is_claimable":false,"name":"Structural Analysis of the Glycoprotein Complex Avidin by Tandem-Trapped Ion Mobility Spectrometry-Mass Spectrometry (Tandem-TIMS/MS).","description":"Glycoproteins play a central role in many biological processes including disease mechanisms. Nevertheless, because glycoproteins are heterogeneous entities, it remains unclear how glycosylation modulates the protein structure and function. Here, we assess the ability of tandem-trapped ion mobility spectrometry-mass spectrometry (tandem-TIMS/MS) to characterize the structure and sequence of the homotetrameric glycoprotein avidin. We show that (1) tandem-TIMS/MS retains native-like avidin tetramers with deeply buried solvent particles; (2) applying high activation voltages in the interface of tandem-TIMS results in collision-induced dissociation (CID) of avidin tetramers into compact monomers, dimers, and trimers with cross sections consistent with X-ray structures and reports from surface-induced dissociation (SID); (3) avidin oligomers are best described as heterogeneous ensembles with (essentially) random combinations of monomer glycoforms; (4) native top-down sequence analysis of the avidin tetramer is possible by CID in tandem-TIMS. Overall, our results demonstrate that tandem-TIMS/MS has the potential to correlate individual proteoforms to variations in protein structure.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Mar","modification":"2025-04-04T01:45:56.278Z","creation":"2025-04-04T01:45:56.278Z"},"accession":"S-EPMC7339587","cross_references":{"pubmed":["32083467"],"doi":["10.1021/acs.analchem.9b05481"]}}