title: Deletion of the propeptide from human preproapolipoprotein A-II redirects cotranslational processing by signal peptidase.
abstract: The functions of NH2-terminal propeptides are not known. We have used apoA-II as a model to study prosegment structure/function relationships. The primary translation product of human apolipoprotein A-II mRNA contains an 18-amino acid signal peptide, a 5-amino acid propeptide, and the mature 77-amino acid plasma protein sequence. Its propeptide was deleted by site-directed mutagenesis of a cloned cDNA. The effects of this mutation on cotranslational translocation and proteolytic processing were assessed using an in vitro transcription/translation/microsomal membrane processing system. Deletion of the propeptide did not affect cotranslational translocation. However, without its propeptide, signal peptidase cleavage was redirected to a different site located between the 2nd and 3rd residues of the mature protein. Since the primary structure of the signal peptide was not altered in the mutant, these results suggest that sequences located downstream from the signal peptidase cleavage site (e.g. in propeptides) may modulate, or participate in defining, the correct site of cotranslational proteolytic processing.
mesh_terms: D001054:Apolipoproteins A / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D005796:Genes; D006801:Humans; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D008957:Models, Genetic; D009154:Mutation; D010957:Plasmids; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012697:Serine Endopeptidases; D014158:Transcription, Genetic
chemical_list: D001054:Apolipoproteins A; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; C039768:preproapolipoprotein A-II; D004247:DNA; D010450:Endopeptidases; D012697:Serine Endopeptidases; C026515:type I signal peptidase