Conformation of the propeptide domain of factor IX.

The propeptide domain in the precursor forms of blood clotting proteins contains the recognition sequences for gamma-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 alpha-helical structure in a 40% trifluoroethanol-containing aqueous solution. The results suggest that the amphipathic alpha-helix within the propeptide domain of factor IX could create a recognition surface for gamma-carboxylase. The influences of mutations and their relationship with the alpha-helical structure are discussed.