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Appendix Prion Protein (PrP) and Doppel (Dpl) Sequences

Kurt Giles, Stanley B. Prusiner


The first complete PrP sequences were reported in 1986 (Basler et al. 1986; Locht et al. 1986). Since then, the PrP genes from more than 100 species have been sequenced. PrP orthologs have been observed in a wide variety of terrestrial vertebrates, representatives of which are shown in Table 1. Full and partial sequences from many other species are available, particularly for primates, ungulates, and rodents (Schätzl et al. 1995; Wopfner et al. 1999; van Rheede et al. 2003).

The discovery of a PrP paralog, termed “doppel” for “downstream, prion protein-like,” which has a tertiary structure similar to that of PrP (Mo et al. 2001) but only ~25% sequence identity (Moore et al. 1999), promises to advance the understanding of PrP function and its role in neurodegeneration. To date, Dpl has been reported only in placental mammals (Table 2).

In the annotated sequence alignment of PrP and Dpl (Fig. 1), the conservation of secondary structure (above sequences) and disulfide bonds (below sequences) between the two proteins is highlighted. Rectangles delineate the predicted signal sequences for translocation (amino termini) and GPI anchor addition (carboxyl termini). Secondary structure, (cylinders) α-helices; (arrows) β-strands; (solid lines) no regular secondary structure; (dashed lines) undetermined structure, is based on a consensus of wild-type structures determined by NMR spectroscopy of human (Zahn et al. 2000), mouse (Rick et al. 1996), Syrian hamster (James et al. 1997), and cow PrP (López García 2000); mouse (Mo et al. 2001) and human Dpl (Lührs et al. 2003). The predominant polymorphic...

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