Open AccessExploring the function of factor XIII free B subunit: Interactions with complement factors and a novel approach to identify potential binding partners
Author(s) -
Li Bojun,
Bechtler Clément,
Jenny Lorenz,
Ricklin Daniel,
Schroeder Verena
Publication year - 2022
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12766
Subject(s) - factor h , complement system , protein subunit , plasma protein binding , complement factor i , chemistry , immunoprecipitation , complement factor b , fibrinogen , cofactor , binding site , alternative complement pathway , biochemistry , biology , antibody , immunology , enzyme , gene
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 α 2 ‐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.