PXD042225 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Plasminogen proteoform profiling |
Description | Plasminogen, the zymogen of plasmin, is a glycoprotein involved in fibrinolysis and a wide variety of other physiological processes. Plasminogen dysregulation has been implicated in a range of diseases. Classically, human plasminogen is categorized into two types based on the presence (type I) or absence (type II) of a single N-linked glycan, supposedly having different functional features. Using high-resolution native mass spectrometry (native MS), we uncover that the proteoform profiles of plasminogen (and plasmin) are substantially more extensive than this simple binary classification. In samples derived from human plasma, we identified up to 14 distinct proteoforms of human plasminogen, including a novel, highly abundant phosphorylation site at Ser339. To elucidate potential functional effects of these post-translational modifications, we performed proteoform-resolved kinetic analyses of the plasminogen-to-plasmin conversion using a canonical activator. This conversion is thought to involve at least two independent cleavage events: one to remove the N-terminal peptide, and another to form the active catalytic site. Our analyses reveal that these processes are not independent but are instead tightly regulated and occur in a step-wise order. Notably, N-terminal cleavage at the canonical site (Lys77) does not occur directly from intact plasminogen. Instead, an activation intermediate corresponding to cleavage at Arg68 is initially produced, which only then is further processed to the canonical Lys77 product. Based on our results, we propose a new categorization system for human plasminogen isoforms. This work highlights the capacity of high-resolution native MS to reveal new aspects of structure, even in frequently-studied serum glycoproteins. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-24 |
AnnouncementXML | Submission_2024-05-24_02:07:44.759.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Dario Cramer |
SpeciesList | scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | phosphorylated residue; complex glycosylation |
Instrument | TripleTOF 5600; Orbitrap Fusion; Q Exactive Plus |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-05-15 03:04:22 | ID requested | |
⏵ 1 | 2024-05-24 02:07:45 | announced | |
Publication List
10.1016/j.mcpro.2023.100696; |
Cramer DAT, Yin V, Caval T, Franc V, Yu D, Wu G, Lloyd G, Langendorf C, Whisstock JC, Law RHP, Heck AJR, Proteoform-Resolved Profiling of Plasminogen Activation Reveals Novel Abundant Phosphorylation Site and Primary N-Terminal Cleavage Site. Mol Cell Proteomics, 23(1):100696(2024) [pubmed] |
Keyword List
submitter keyword: Plasminogen Serum PTM |
Contact List
Albert J. R. Heck |
contact affiliation | Biomolecular Mass Spectrometry and Proteomics, Utrecht University, Utrecht, The Netherlands |
contact email | a.j.r.heck@uu.nl |
lab head | |
Dario Cramer |
contact affiliation | Utrecht University |
contact email | d.a.t.cramer@uu.nl |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD042225
- Label: PRIDE project
- Name: Plasminogen proteoform profiling