Next Article in Journal / Special Issue
Prion Strains and Transmission Barrier Phenomena
Previous Article in Journal
PqsA Promotes Pyoverdine Production via Biofilm Formation
Previous Article in Special Issue
Recombinant PrP and Its Contribution to Research on Transmissible Spongiform Encephalopathies
Open AccessPerspective

The Evolutionary unZIPping of a Dimerization Motif—A Comparison of ZIP and PrP Architectures

by Jian Hu 1,2, Holger Wille 3,4 and Gerold Schmitt-Ulms 5,6,*
1
Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
2
Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA
3
Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2M8, Canada
4
Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, AB T6G 2M8, Canada
5
Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON M5T 2S8, Canada
6
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada
*
Author to whom correspondence should be addressed.
Pathogens 2018, 7(1), 4; https://doi.org/10.3390/pathogens7010004
Received: 5 December 2017 / Revised: 20 December 2017 / Accepted: 22 December 2017 / Published: 29 December 2017
(This article belongs to the Special Issue PrPSc prions: state of the art)
The cellular prion protein, notorious for its causative role in a range of fatal neurodegenerative diseases, evolved from a Zrt-/Irt-like Protein (ZIP) zinc transporter approximately 500 million years ago. Whilst atomic structures for recombinant prion protein (PrP) from various species have been available for some time, and are believed to stand for the structure of PrPC, the first structure of a ZIP zinc transporter ectodomain was reported only recently. Here, we compare this ectodomain structure to structures of recombinant PrP. A shared feature of both is a membrane-adjacent helix-turn-helix fold that is coded by a separate exon in the respective ZIP transporters and is stabilized by a disulfide bridge. A ‘CPALL’ amino acid motif within this cysteine-flanked core domain appears to be critical for dimerization and has undergone stepwise regression in fish and mammalian prion proteins. These insights are intriguing in the context of repeated observations of PrP dimers. Other structural elements of ZIP transporters and PrP are discussed with a view to distilling shared versus divergent biological functions. View Full-Text
Keywords: ZIP metal ion transporter; prion protein; dimerization; evolution ZIP metal ion transporter; prion protein; dimerization; evolution
Show Figures

Graphical abstract

MDPI and ACS Style

Hu, J.; Wille, H.; Schmitt-Ulms, G. The Evolutionary unZIPping of a Dimerization Motif—A Comparison of ZIP and PrP Architectures. Pathogens 2018, 7, 4.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop