Uncoupling of co-translational translocation from signal peptidase processing in a mutant rat preapolipoprotein-A-IV with a deletion that includes the COOH-terminal region of its signal peptide

S. F. Nothwehr, R. J. Folz, J. I. Gordon

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In order to characterize the function of the COOH-terminal (c) region of eukaryotic signal peptides, a 14-amino acid long segment was deleted from a secreted rat liver and intestinal protein, preapolipoprotein-A-IV. This deletion spanned the c-region plus all potential signal peptidase cleavage sites. The functional consequences of this mutation were assessed using an in vitro transcription/translation/microsomal membrane processing system. Removal of these residues had no effect on interaction of the nascent preprotein with signal recognition particle as measured by a translational arrest assay. Although no signal peptidase cleavage of the mutant was detected, the efficiency of its co-translational translocation was similar to the wild type protein. A postinitiation translocation assay was utilized to compare the translocation capabilities of nascent wild type and mutant proteins as their chain lengths were progressively increased. No difference was detected between the two species suggesting that their initial conformations are functionally equivalent as measured by the translocation machinery. We conclude from these studies of preapolipoprotein-A-IV that (i) the efficiency of translocation is not dependent on signal peptidase cleavage and (ii) structural features present in the c-region of the signal peptide are not necessary for interaction with signal recognition particle or for subsequent targeting to, and translocation across, microsomal membranes.

Original languageEnglish (US)
Pages (from-to)4642-4647
Number of pages6
JournalJournal of Biological Chemistry
Volume264
Issue number8
StatePublished - 1989

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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