Mass spectrometry– based molecular mapping of native FXIIIa cross-links in insoluble fibrin clots

Lauren R. Schmitt, Rachel Henderson, Alexander Barrett, Zsuzsanna Darula, Aaron Issaian, Angelo D’Alessandro, Nathan Clendenen, Kirk C. Hansen

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2 Citations (Scopus)

Abstract

The roles of factor XIIIa–specific cross-links in thrombus formation, regression, or probability for embolization are largely unknown. A molecular understanding of fibrin architecture at the level of these cross-links could inform the development of therapeutic strategies to prevent the sequelae of thromboembolism. Here, we present an MS-based method to map native factor XIIIa cross-links in the insoluble matrix component of whole-blood or plasma-fibrin clots and in in vivo thrombi. Using a chaotrope-insoluble digestion method and quantitative crosslinking MS, we identified the previously mapped fibrinogen peptides that are responsible for covalent D-dimer association, as well as dozens of novel cross-links in the C region of fibrinogen . Our findings expand the known native cross-linked species from one to over 100 and suggest distinct antiparallel registries for interprotofibril association and covalent attachment of serpins that regulate clot dissolution.

Original languageEnglish
Pages (from-to)8773-8778
Number of pages6
JournalJournal of Biological Chemistry
Volume294
Issue number22
DOIs
Publication statusPublished - May 31 2019

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Schmitt, L. R., Henderson, R., Barrett, A., Darula, Z., Issaian, A., D’Alessandro, A., Clendenen, N., & Hansen, K. C. (2019). Mass spectrometry– based molecular mapping of native FXIIIa cross-links in insoluble fibrin clots. Journal of Biological Chemistry, 294(22), 8773-8778. https://doi.org/10.1074/jbc.AC119.007981