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


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 cross-linking 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.

SUBMITTER: Schmitt LR 

PROVIDER: S-EPMC6552431 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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

Schmitt Lauren R LR   Henderson Rachel R   Barrett Alexander A   Darula Zsuzsanna Z   Issaian Aaron A   D'Alessandro Angelo A   Clendenen Nathan N   Hansen Kirk C KC  

The Journal of biological chemistry 20190426 22


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 <i>in vivo</i> thrombi. Using  ...[more]

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