Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease.

摘要: The primary translation product of human intestinal apolipoprotein A-I mRNA was isolated from wheat germ and ascites cell-free systems. Comparison its NH2-terminal sequence with that plasma high density lipoprotein-associated showed it is initially synthesized as a preproprotein. Like rat preproapolipoprotein A-I, contains an 18-amino acid prepeptide 6-amino propeptide. highly unusual COOH-terminal Gln-Gln dipeptide present in the pro-segment also represented at same position sequence. functional division 24-amino extention into pro- presegments verified by finding stable intracellular form hepatoma cell line proprotein. Edman degradation radiolabeled extracellular indicated this secreted without proteolytic cleavage hexapeptide prosegment. Therefore, appears undergoes additional processing step before fully integrated lipoprotein. Two-dimensional gel electrophoresis purified proapolipoprotein hepatocyte culture media corresponds to isoforms 2 3, basic isoproteins which are precursors predominant found patients Tangier's disease (Zannis, V. I., Lees, A. M., R. S., Breslow, J. L. (1982) Biol. Chem., 257, 4978-4986). Therefore pathologic state probably arises defect conversion A-I.