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Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters

In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interac...

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Autores principales: Schmitt-Ulms, Gerold, Ehsani, Sepehr, Watts, Joel C., Westaway, David, Wille, Holger
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745754/
https://www.ncbi.nlm.nih.gov/pubmed/19784368
http://dx.doi.org/10.1371/journal.pone.0007208
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author Schmitt-Ulms, Gerold
Ehsani, Sepehr
Watts, Joel C.
Westaway, David
Wille, Holger
author_facet Schmitt-Ulms, Gerold
Ehsani, Sepehr
Watts, Joel C.
Westaway, David
Wille, Holger
author_sort Schmitt-Ulms, Gerold
collection PubMed
description In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease.
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spelling pubmed-27457542009-09-28 Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters Schmitt-Ulms, Gerold Ehsani, Sepehr Watts, Joel C. Westaway, David Wille, Holger PLoS One Research Article In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease. Public Library of Science 2009-09-28 /pmc/articles/PMC2745754/ /pubmed/19784368 http://dx.doi.org/10.1371/journal.pone.0007208 Text en Schmitt-Ulms et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schmitt-Ulms, Gerold
Ehsani, Sepehr
Watts, Joel C.
Westaway, David
Wille, Holger
Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title_full Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title_fullStr Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title_full_unstemmed Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title_short Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters
title_sort evolutionary descent of prion genes from the zip family of metal ion transporters
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745754/
https://www.ncbi.nlm.nih.gov/pubmed/19784368
http://dx.doi.org/10.1371/journal.pone.0007208
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