Biosynthesis of human preapolipoprotein A-IV.
The primary translation product of human intestinal apolipoprotein A-IV mRNA was purified from ascites and wheat germ cell-free systems. Comparison of its NH2-terminal sequence with mature, chylomicron-associated apo-A-IV revealed that apo-A-IV was initially synthesized with a 20-amino acid long NH2-terminal extension: Met-X-Leu-X-Ala-Val-Val-Leu-X-Leu-Ala-Leu-Val-Ala-Val-Ala-Leu-X-X-Ala. Co-translational cleavage of the cell-free product as well as Edman degradation of the stable intracellular form of the protein recovered from Hep G2 cells indicated that this entire 20-amino acid sequence behaved as a signal peptide. There is at least 55% sequence homology between the rat and human apo-A-IV signal peptides and 33% homology between the human A-I and A-IV presegments. Agarose gel chromatography of Hep G2 culture media indicated that neither apo-A-IV nor -A-I is associated with particles that have physical properties resembling any of the plasma lipoprotein density classes. Incubation of plasma with Hep G2 media resulted in transfer of A-I but not A-IV to lipoproteins. Since the NH2 termini of co-translationally cleaved and chylomicron-associated apo-A-IV are identical, it is apparent that 1) this polypeptide does not undergo NH2-terminal post-translational proteolysis like proapo-A-II or proapo-A-I, and 2) regulation of A-IV-lipoprotein interaction is not dependent on any NH2-terminal proteolytic processing event.
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000096:biosynthesis*; D001054:Apolipoproteins A; D002474:Cell-Free System; D002850:Chromatography, Gel; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008970:Molecular Weight; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism
D001053:Apolipoproteins; D001054:Apolipoproteins A; D011498:Protein Precursors; D012333:RNA, Messenger; C022205:apolipoprotein A-IV