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Recombinant scrapie-like prion protein of 106 amino acids is soluble

By Tamaki Muramoto, Michael Scott, Fred E. Cohen and Stanley B. Prusiner

Abstract

The N terminus of the scrapie isoform of prion protein (PrP(Sc)) can be truncated without loss of scrapie infectivity and, correspondingly, the truncation of the N terminus of the cellular isoform, PrP(C), still permits conversion into PrP(Sc). To assess whether additional segments of the PrP molecule can be deleted, we previously removed regions of putative secondary structure in PrP(C); in the present study we found that deletion of each of the four predicted helices prevented PrP(Sc) formation, as did deletion of the stop transfer effector region and the C178A mutation. Removal of a 36-residue loop between helices 2 and 3 did not prevent formation of protease-resistant PrP; the resulting scrapie-like protein, designated PrP(Sc)106, contained 106 residues after cleavage of an N-terminal signal peptide and a C-terminal sequence for glycolipid anchor addition. Addition of the detergent Sarkosyl to cell lysates solubilized PrP(Sc)106, which retained resistance to digestion by proteinase K. These results suggest that all the regions of proposed secondary structure in PrP are required for PrP(Sc) formation, as is the disulfide bond stabilizing helices 3 and 4. The discovery of PrP(Sc)106 should facilitate structural studies of PrP(Sc), investigations of the mechanism of PrP(Sc) formation, and the production of PrP(Sc)-specific antibodies

Topics: Biological Sciences
Publisher: The National Academy of Sciences of the USA
Year: 1996
OAI identifier: oai:pubmedcentral.nih.gov:26426
Provided by: PubMed Central
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