Abstract Number: LPB0111
Meeting: ISTH 2021 Congress
Background: Coagulation factor XIII (FXIII) consists of two potentially active A subunits and two inhibitory/protective B subunits (FXIII-A2B2). FXIII-B is in excess, half of it circulates in non-complexed form. It contains 8.5 % carbohydrate; the glycan part has a role in keeping FXIII-A2B2 in the circulation. A major polymorphism of FXIII-B is due to a novel splice acceptor site in intron K (IK) and the replacement of 10 C-terminal amino acids by 25 novel amino acids. FXIII-B is associated to fibrinogen through fibrinogen γ-chain. Peak 1 fibrinogen (P1F; 85% of plasma fibrinogen) contains two γA-chains, peak 2 fibrinogen (P2F) also posseses alternatively spliced γ‘-chain.
Aims: To evaluate whether the glycan residue and FXIII-B IK polymorphism influence the binding of FXIII-B to FXIII-A and how FXIII-B and its polymorphic variant binds to P1F and P2F.
Methods: Binding studies between proteins and large peptides were carried out by surface plasmon resonance technique. Association rate constant (ka), dissociation rate constants (kd), and equilibrium dissociation constants (Kd) were calculated. Association of a short γA-chain peptide to FXIII-B was investigated by isothermal titration calorimetry (ITC).
|Table 1 Surface plasmon resonance results|
|Ligand||Analite||ka (1/Ms)||kd (1/s)||Kd (M)|
|FXIII-B||rFXIII-A||1.17 x 105±2.36 x 104||7.64 x 10-4±9.31 x 10-5||6.80 x 10-9±1.86 x 10-9|
|IK-FXIII-B||rFXIII-A||1.03 x 105±3.16 x 104||7.81 x 10-4±7.21 x 10-5||8.43 x 10-9±3.62 x 10-9|
|DG-FXIII-B||rFXIII-A||7.32 x 104±3.24 x 104||2.11 x 10-3±8.76 x 10-4||3.06 x 10-8±8.63 x 10-9|
|FXIII-B||FXIII-B||2.28 x 104±1.37 x 104||5.29 x 10-4±9.14 x 10-5||2.75 x 10-8±9.89 x 10-9|
|Peak1 fibrinogen||FXIII-B||1.47 x 104±9.32 x 103||2.79 x 10-3±2.79 x 10-3||5.03 x 10-7±7.68 x 10-7|
|Peak2 fibrinogen||FXIII-B||1.11 x 105±1.29 x 105||1.89 x 10-3±2.06 x 10-4||2.89 x 10-8±1.12 x10-7|
|IK-FXIII-B||Peak1 fibrinogen||3.76 x 103±8.32 x 102||1.22 x 10-2±1.36 x 10-3||3.36 x 10-6±6.29 x 10-7|
|IK-FXIII-B||Peak2 fibrinogen||4.45 x 104±8.92 x 104||1.31 x 10-3±2.33 x 10-3||8.17 x 10-7±1.97 x 10-6|
|γ’ sulfated peptide||FXIII-B||1.75 x 104±6.70 x 103||1.17 x 10-3±3.80 x 10-5||7.42 x 10-8±2.48 x 10-8|
|γ’ non-sulfated peptide||FXIII-B||1.95 x 104±2.25 x 104||1.27 x 10-3±2.29 x 10-4||1.68 x 10-7±1.78 x 10-7|
Deglycosylated FXIII-B (DG-FXIII-B) showed decreased affinity to FXIII-A. The Kd for the binding of native and IK FXIII-B variant to FXIII-A were comparable. Interestingly, FXIII-B as analyte also bound to the ligand FXIII-B (Kd=2.75×10-8). FXIII-B bound to P2F with somewhat higher affinity than to P1F (Kd=2.89×10-8 versus Kd=5.03×10-7). Using ITC, we confirmed the results of Byrnes et al. (Blood 2016;128:1969-78) demonstrating that the C-terminal peptide of γA-chain, which is also present in the γ’-chain binds to FXIII-B (Kd=2.40×10-8). However, the sulfated peptide part of the γ‘-chain also showed relatively high affinity toward FXIII-B (Kd=7.42×10-8).
Conclusions: The results suggest that the glycan structure of FXIII-B contributes to its binding to FXIII-A and FXIII-B associates to both types of fibrinogen chains.
To cite this abstract in AMA style:Pénzes K, Bécsi B, Erdődi F, Muszbek L. Molecular Interactions of Coagulation Factor XIII B Subunit [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/molecular-interactions-of-coagulation-factor-xiii-b-subunit/. Accessed December 11, 2023.
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