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Optimization of plasma-based BioID identifies plasminogen as a ligand of ADAMTS13

Authors :
Hasam Madarati
Veronica DeYoung
Kanwal Singh
Taylor Sparring
Andrew C. Kwong
James C. Fredenburgh
Cherie Teney
Marlys L. Koschinsky
Michael B. Boffa
Jeffrey I. Weitz
Colin A. Kretz
Source :
Scientific Reports, Vol 14, Iss 1, Pp 1-12 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract ADAMTS13, a disintegrin and metalloprotease with a thrombospondin type 1 motif, member 13, regulates the length of Von Willebrand factor (VWF) multimers and their platelet-binding activity. ADAMTS13 is constitutively secreted as an active protease and is not inhibited by circulating protease inhibitors. Therefore, the mechanisms that regulate ADAMTS13 protease activity are unknown. We performed an unbiased proteomics screen to identify ligands of ADAMTS13 by optimizing the application of BioID to plasma. Plasma BioID identified 5 plasma proteins significantly labeled by the ADAMTS13-birA* fusion, including VWF and plasminogen. Glu-plasminogen, Lys-plasminogen, mini-plasminogen, and apo(a) bound ADAMTS13 with high affinity, whereas micro-plasminogen did not. None of the plasminogen variants or apo(a) bound to a C-terminal truncation variant of ADAMTS13 (MDTCS). The binding of plasminogen to ADAMTS13 was attenuated by tranexamic acid or ε-aminocaproic acid, and tranexamic acid protected ADAMTS13 from plasmin degradation. These data demonstrate that plasminogen is an important ligand of ADAMTS13 in plasma by binding to the C-terminus of ADAMTS13. Plasmin proteolytically degrades ADAMTS13 in a lysine-dependent manner, which may contribute to its regulation. Adapting BioID to identify protein-interaction networks in plasma provides a powerful new tool to study protease regulation in the cardiovascular system.

Details

Language :
English
ISSN :
20452322
Volume :
14
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Scientific Reports
Publication Type :
Academic Journal
Accession number :
edsdoj.6c1de69cded4b81ba05feac596653ea
Document Type :
article
Full Text :
https://doi.org/10.1038/s41598-024-59672-6