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Science 13 April 1990:
Vol. 248. no. 4952, pp. 226 - 229
DOI: 10.1126/science.1970195
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Articles

Science, Vol 248, Issue 4952, 226-229
Copyright © 1990 by American Association for the Advancement of Science

articles

Unusual topogenic sequence directs prion protein biogenesis

CD Lopez, CS Yost, SB Prusiner, RM Myers, and VR Lingappa

Department of Physiology, University of California, San Francisco 94143.

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.


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