PXD042225-1

PXD042225 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-15 03:04:22	ID requested
⏵ 1	2024-05-24 02:07:45	announced

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]

submitter keyword: Plasminogen Serum PTM

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

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.pride.ebi.ac.uk/pride/data/archive/2024/05/PXD042225

PRIDE project URI

• PRIDE
  1. PXD042225
     1. Label: PRIDE project
     2. Name: Plasminogen proteoform profiling