Unusual topogenic sequence directs prion protein biogenesis

Academic Article

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.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Lopez CD; Yost CS; Prusiner SB; Myers RM; Lingappa VR
  • Start Page

  • 226
  • End Page

  • 229
  • Volume

  • 248
  • Issue

  • 4952