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Evolutionary descent of prion genes from a ZIP metal ion transport ancestor

Gerold Schmitt-Ulms¹, Sepehr Ehsani¹, Joel C. Watts², David Westaway³ & Holger Wille²

Correspondence: (Login to view email address)

1. University of Toronto
2. University of California, San Francisco
3. University of Alberta

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Document Type:

Manuscript

Date:

Received 10 February 2009 21:16 UTC; Posted 10 February 2009

Subjects:

Genetics & Genomics, Molecular Cell Biology, Evolutionary Biology

Tags:

• mass spectrometry
• ZIP
• structure
• interactome
• CJD
• Slc39a
• Prion
• iTRAQ
• alignment

Abstract:

In the more than 20 years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into the function of PrP may be obtained through a characterization of its molecular neighborhood. Quantitative interactome data revealed the spatial proximity of a subset of metal ion transporters of the ZIP family to mammalian prion proteins. A subsequent bioinformatic analysis revealed the presence of a prion-like protein sequence within the N-terminal, extracellular domain of a phylogenetic branch of ZIPs. Additional structural threading and ortholog sequence alignment analyses consolidated the conclusion that the prion protein gene family is phylogenetically derived from a ZIP-like ancestor molecule. Our data explain structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The connection to ZIP proteins is expected to open new avenues to elucidate the biology of the prion protein in health and disease.

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License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Schmitt-Ulms, Gerold, Ehsani, Sepehr, Watts, Joel, Westaway, David, and Wille, Holger. Evolutionary descent of prion genes from a ZIP metal ion transport ancestor. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2009.2867.1> (2009)

Version info:

Published version:

10.1371/journal.pone.0007208 (Peer Reviewed) PLoS One. 2009 Sep 28;4(9):e7208. PMID: 19784368

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