CONFORMATION OF THE PROPEPTIDE DOMAIN OF FACTOR-IX

The propeptide domain in the precursor forms of blood clotting protein s contains the recognition sequences for gamma-carboxylase. In hemophi lia B, several point mutations in this propeptide domain are responsib le for the inherited disease. A peptide containing the propeptide sequ ence of factor IX was synthesized by solid phase methods. Two dimensio nal H-1-NMR and CD studies indicate that this peptide motif adopts an alpha-helical structure in a 40% trifluoroethanol-containing aqueous s olution. The results suggest that the amphipathic alpha-helix within t he propeptide domain of factor IX could create a recognition surface f or gamma-carboxylase. The influences of mutations and their relationsh ip with the alpha-helical structure are discussed.