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Thromb Haemost 1996; 75(01): 070-075
DOI: 10.1055/s-0038-1650223
Original Article
Schattauer GmbH Stuttgart

Mutations which Introduce Free Cysteine Residues in the Gla-Domain of Vitamin K Dependent Proteins Result in the Formation of Complexes with α1-Microglobulin

E G C Wojcik
The Haemostasis and Thrombosis Research Centre, University Hospital Leiden, The Netherlands
,
P Simioni
1   The Institute of Medical Semeiotics, IV Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
M v d Berg
The Haemostasis and Thrombosis Research Centre, University Hospital Leiden, The Netherlands
,
A Girolami
1   The Institute of Medical Semeiotics, IV Chair of Internal Medicine, University of Padua Medical School, Padua, Italy
,
R M Bertina
The Haemostasis and Thrombosis Research Centre, University Hospital Leiden, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 17 May 1995

Accepted after revision 21 September 1995

Publication Date:
10 July 2018 (online)

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Summary

We have previously described a genetic factor IX variant (Cys18→Arg) for which we demonstrated that it had formed a heterodimer with armicroglobulin through formation of a disulphide bond with the remaining free cysteine residue of the disrupted disulphide bond in the Gla-domain of factor IX. Recently, we observed a similar high molecular weight complex for a genetic protein C variant (Arg-1→Cys). Both the factor IX and the protein C variants have a defect in the calcium induced conformation. In this study we show that the aminoterminus of this protein C variant is prolonged with one amino acid, cysteine. This protein C variant, as well as protein C variants with Arg9→Cys and Ser12→Cys mutations which also carry a free cysteine residue, are shown to be present in plasma as a complex with α1-microglobulin. A prothrombin variant with a Tyr44→Cys mutation, had not formed such a complex. Furthermore, complexes between normal vitamin K-dependent clotting factors and α1-microglobulin were shown to be present in plasma at low concentrations. The data suggest that the presence of an unpaired cysteine residue in the propeptide or the N-terminal half of the Gla-domain has strongly promoted the formation of a complex with α1-microglobulin in the variants.

 

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