These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Processing of flavivirus structural glycoproteins: stable membrane insertion of premembrane requires the envelope signal peptide.
    Author: Markoff L, Chang A, Falgout B.
    Journal: Virology; 1994 Nov 01; 204(2):526-40. PubMed ID: 7941319.
    Abstract:
    The flavivirus structural proteins capsid (C), premembrane (prM), and envelope (E) are cleaved in that order from the N-terminus of the polyprotein by the ER intralumenal enzyme signal peptidase. The prM-E and E-NS1 junctions contain hydrophobic domains with both transmembrane and signal function. These domains reside at the C-termini of prM and E, respectively, after cleavage. We studied the functions of the 37-amino-acid C-terminus of the dengue virus type 4 (DEN4) prM (amino acids 243-279 of the DEN4 polyprotein) in the processing of prM and E. Hydrophobicity in this domain is interrupted by a conserved Arg residue (Arg-264) within a short amphipathic segment. Hydrophobic amino acids upstream from Arg-264 (aa 243-263) were presumed to constitute the membrane anchor for prM (the "tm" segment). Previous results had suggested that sequences downstream from Arg-264 (aa 265-279) constitute the E signal peptide. RNA transcripts prepared from wild-type (wt) and deletion-mutant DEN4 cDNAs encoding the prM signal peptide, prM, E, and the N-terminus of the nonstructural glycoprotein, NS1, were translated in rabbit reticulocyte lysate in the presence of microsomes. Processing of wt prM and E in vitro appeared to mimic processing occurring during flavivirus infection. Analysis of mutants confirmed the localization of the E signal peptide within residues 265 to 279. However, deletions within either the E signal peptide or the tm segment resulted in a defect in both membrane insertion of prM and cleavage of the prM-E junction. Membrane anchoring of prM appeared to be a two-step process requiring function of both the tm segment and the E signal peptide, and fully efficient prM-E cleavage was also dependent upon the integrity of both hydrophobic domains. We propose a model for the processing of the flavivirus structural glycoproteins based on these results.
    [Abstract] [Full Text] [Related] [New Search]