Prion Proteins Appear to Share Evolutionary Origin with ZIP Proteins

Suggestive evidence as to the evolutionary ancestry of prion proteins has been obtained by researchers at the University of Toronto and collaborating institutions. Prions are responsible for such devastating diseases as “mad cow disease” (bovine spongiform encephalopathy) and Creutzfeldt-Jakob disease. The researchers’ analysis suggests that the prion gene is descended from the more ancient ZIP family of metal ion transporters. Members of the ZIP protein family are well known for their ability to transport zinc and other metals across cell membranes. The researchers initially demonstrated the physical proximity of two metal ion transporters, ZIP6 and ZIP10, to mammalian prion proteins in living cells. As with the normal cellular prion protein, ZIP6 and ZIP10 exhibit widespread expression in biological tissues with high transcript levels in the brain. The scientists then made the startling discovery that prion and ZIP proteins contain extensive stretches of similar amino acid sequence. The researchers next documented that the respective segments within ZIP and prion proteins are computationally predicted to acquire a highly similar three-dimensional structure. Finally, the team uncovered multiple additional commonalities between ZIP and prion proteins, which led them to conclude that these molecules are evolutionarily related. Overall, this work holds promise for efforts to reveal the physiological function of members of the prion protein family and may provide insights into the origins and underlying constraints of the conformational changes associated with prion diseases. This work was published on September 28 in PLoS ONE. [Press release] [PLoS ONE article]
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