The propeptide domain in the precursor forms of blood clotting proteins contains the recognition sequences for γ-carboxylase. In hemophilia B, several point mutations in this propeptide domain are responsible for the inherited disease. A peptide containing the propeptide sequence of factor IX was synthesized by solid phase methods. Two dimensional 1H-NMR and CD studies indicate that this peptide motif adopts an α-helical structure in a 40% trifluoroethanol-containing aqueous solution. The results suggest that the amphipathic α-helix within the propeptide domain of factor IX could create a recognition surface for γ-carboxylase. The influences of mutations and their relationship with the α-helical structure are discussed.
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