The Evolutionary unZIPping of a Dimerization Motif—A Comparison of ZIP and PrP Architectures
AbstractThe 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
Scifeed alert for new publicationsNever miss any articles matching your research from any publisher
- Get alerts for new papers matching your research
- Find out the new papers from selected authors
- Updated daily for 49'000+ journals and 6000+ publishers
- Define your Scifeed now
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.
Hu J, Wille H, Schmitt-Ulms G. The Evolutionary unZIPping of a Dimerization Motif—A Comparison of ZIP and PrP Architectures. Pathogens. 2018; 7(1):4.Chicago/Turabian Style
Hu, Jian; Wille, Holger; Schmitt-Ulms, Gerold. 2018. "The Evolutionary unZIPping of a Dimerization Motif—A Comparison of ZIP and PrP Architectures." Pathogens 7, no. 1: 4.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.