PrP-like ectodomain of mouse ZIP5 and pufferfish PrP-1 are predicted to acquire a PrP-like fold.

<p>(<b>A</b>) Multiple sequence alignment of selected prion protein sequences with ZIP5 and ZIP10 orthologs from fish and mice. Of note is the absence of positional alignment but the conservation of a mixed charge character N-terminal to the cysteine-flanked core (CFC) domain. ‘G’ and ‘S’ label sites of glycosylation and disulfide linkages, respectively. The α-helix (designated as ‘H’) and β-strand (designated as ‘E’) secondary structural elements known to exist in mouse PrP^C are marked. Species abbreviations are: Tr; <i>Takifugu rubripes</i>; Dr, <i>Danio rerio</i>; and Mm, <i>Mus musculus</i>. Dr_ZIP5 was included in the multiple alignment since no Tr ortholog has been identified. (<b>B</b>) From left to right, the NMR structure of <i>Xenopus laevis</i> PrP (PDB entry 1xu0), a model of <i>Takifugu rubripes</i> PrP-1 (residues 28–450), a model of the N-terminal extracellular domain of mouse ZIP5 (residues 116–212), and an overlay depicting the NMR structure of <i>Xenopus laevis</i> PrP (green) together with models of Tr_PrP-1 (red) and Mm_ZIP5 (blue) are depicted. In the overlay, stretches of the proteins only shown in one color are in complete overlap amongst the structure and the two models (e.g., parts of α-helices B and C).