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Von Willebrand factor protects the Ca 2+ ‐dependent structure of the factor VIII light chain
Author(s) -
Takeyama Masahiro,
Nogami Keiji,
Okuda Masahiro,
Shima Midori
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07792.x
Subject(s) - immunoglobulin light chain , von willebrand factor , chemistry , microbiology and biotechnology , medicine , platelet , immunology , antibody , biology
Summary We have recently reported that cation‐exchange iminodiacetate resin completely inactivated factor VIII (FVIII) by direct deprivation of metal ions, predominantly Ca 2+ , from its molecules, and that von Willebrand factor (VWF) protected FVIII antigen from resin‐induced degradation. The present study was further developed to investigate this mechanism. Western blotting analysis and enzyme‐linked immunosorbent assay showed that the antigenic structure of the FVIII light chain, especially the C2 domain, was completely impaired by the resin, whilst that of the heavy chain was little affected. However, the complex formation with VWF protected the C2 domain from the resin‐induced degradation. The resin‐treated C2 domain failed to interact with VWF and phospholipid. Furthermore, the addition of Ca 2+ competitively blocked the resin‐induced impairment of the C2 domain structure. These results demonstrate that VWF protects the Ca 2+ ‐dependent conformational structure of the FVIII light chain, especially the C2 domain, and may indicate that the C2 domain contains the Ca 2+ ‐binding site(s).