title: Unusual topogenic sequence directs prion protein biogenesis.
abstract: Biosynthetic studies of the prion protein (PrP) have shown that two forms of different topology can be generated from the same pool of nascent chains in cell-free translation systems supplemented with microsomal membranes. A transmembrane form is the predominant product generated in wheat germ (WG) extracts, whereas a completely translocated (secretory) form is the major product synthesized in rabbit reticulocyte lysates (RRL). An unusual topogenic sequence within PrP is now shown to direct this system-dependent difference. The actions of this topogenic sequence were independent of on-going translation and could be conferred to heterologous proteins by the engineering of a discrete set of codons. System-dependent topology conferred by addition of RRL to WG translation products suggests that this sequence interacts with one or more cytosolic factors.
authors.affiliation: Department of Physiology, University of California, San Francisco 94143.
authors.forename: C D
authors.initials: CD
authors.lastname: Lopez
authors.forename: C S
authors.initials: CS
authors.lastname: Yost
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: R M
authors.initials: RM
authors.lastname: Myers
authors.forename: V R
authors.initials: VR
authors.lastname: Lingappa
mesh_terms: D000818:Animals; D003062:Codon; D006224:Cricetinae; D004279:DNA, Viral / Q000235:genetics; D007700:Kinetics; D008647:Mesocricetus; D010449:Peptide Mapping; D010957:Plasmids; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics*; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D003062:Codon; D004279:DNA, Viral; D018620:PrPSc Proteins; D011328:Prions; D014764:Viral Proteins