Exploring the function of factor XIII free B subunit: Interactions with complement factors and a novel approach to identify potential binding partners.

Li, Bojun; Bechtler, Clément; Jenny, Lorenz; Ricklin, Daniel; Schroeder, Verena (2022). Exploring the function of factor XIII free B subunit: Interactions with complement factors and a novel approach to identify potential binding partners. Research and practice in thrombosis and haemostasis, 6(5), e12766. Wiley 10.1002/rth2.12766

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Background

The factor XIII (FXIII)-B subunit has a critical function as a carrier protein to stabilize FXIII-A in plasma and supply it to its main substrate, fibrinogen. However, the function of the excess free FXIII-B circulating in plasma is still elusive.

Objectives

In the present study, we explored potential interactions of free FXIII-B with complement factors and searched for novel binding partners.

Methods

We tested for cofactor activity in the degradation of complement C3b and C4b and used ELISA- and surface plasmon resonance-based binding assays to investigate interactions between FXIII-B and complement components. We performed immunoprecipitation and mass spectrometry analysis to identify potential binding partners of free FXIII-B in freshly drawn plasma samples.

Results

FXIII-B did not exhibit cofactor activity in the degradation of C3b and C4b similar to factor H and C4b-binding protein, nor did it bind to complement factors to a relevant extent. Identification of proteins potentially binding to free FXIII-B revealed high interindividual variation. We confirmed α2-macroglobulin (α2MG) as a candidate, although direct interactions or functional effects remain to be validated.

Conclusions

Our study reveals that free FXIII-B has no direct role in regulating the complement system, despite a structural similarity to major complement regulators. Further studies are needed to validate α2MG as a binding partner and explore potential functional consequences of this binding.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Experimentelle Hämostase
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Li, Bojun; Jenny, Lorenz and Schröder, Verena

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2475-0379

Publisher:

Wiley

Language:

English

Submitter:

Pubmed Import

Date Deposited:

28 Jul 2022 12:00

Last Modified:

31 Jul 2022 01:58

Publisher DOI:

10.1002/rth2.12766

PubMed ID:

35873217

Uncontrolled Keywords:

coagulation factor XIII complement system factor XIII B‐subunit α 2‐macroglobulin

BORIS DOI:

10.48350/171541

URI:

https://boris.unibe.ch/id/eprint/171541

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