Abstract
Prion diseases are a group of rare neurodegenerative disorders that develop as a result of the conformational conversion of normal prion protein (PrPC) to the disease-associated isoform (PrPSc). The mechanism that actually causes disease remains unclear. However, the mechanism underlying the conformational transformation of prion protein is partially understood—in particular, there is strong evidence that copper ions play a significant functional role in prion proteins and in their conformational conversion. Various models of the interaction of copper ions with prion proteins have been proposed for the Cu (II)-binding, cell-surface glycoprotein known as prion protein (PrP). Changes in the concentration of copper ions in the brain have been associated with prion diseases and there is strong evidence that copper plays a significant functional role in the conformational conversion of PrP. Nevertheless, because copper ions have been shown to have both a positive and negative effect on prion disease onset, the role played by Cu (II) ions in these diseases remains a topic of debate. Because of the unique properties of paramagnetic Cu (II) ions in the magnetic field, their interactions with PrP can be tracked even at single atom resolution using nuclear magnetic resonance (NMR) spectroscopy. Various NMR approaches have been utilized to study the kinetic, thermodynamic, and structural properties of Cu (II)-PrP interactions. Here, we highlight the different models of copper interactions with PrP with particular focus on studies that use NMR spectroscopy to investigate the role played by copper ions in prion diseases.
Highlights
Prion diseases are a family of rare and progressive neurodegenerative disorders that develop as a result of the conformational conversion of the normal form of the transmissible prion protein (PrPC) into the disease-associated form (PrPSc) [1]
Prion proteins are highly conserved among mammals [3, 4], where the general structure of globular domain protein, Normal prion protein (PrPC) contains three αhelices and a two-strand antiparallel β-sheets, an NH2-terminal tail consisting of an octapeptide repeat-containing unfolded domain, and GPI attached to the short COOHterminal tail [5]
Structural biology approaches, in general, and nuclear magnetic resonance (NMR) spectroscopy, in particular, have the potential to be very useful in the study of copper ion coordination with PrP to help elucidate the role played by copper ions in prion diseases [116]
Summary
Prion diseases are a family of rare and progressive neurodegenerative disorders that develop as a result of the conformational conversion of the normal form of the transmissible prion protein (PrPC) into the disease-associated form (PrPSc) [1]. Structural biology approaches, in general, and NMR spectroscopy, in particular, have the potential to be very useful in the study of copper ion coordination with PrP to help elucidate the role played by copper ions in prion diseases [116]. There are several limitations to the use of NMR spectroscopy as an analytical tool to study the interaction between copper ions and prion proteins. To elucidate the role of copper in prion diseases, further investigations should be conducted to study the relationship between electron transfer reactions and the conformational transformation associated with copper-protein interactions. The NMR spectroscopy offers atomiclevel insights into the interactions of copper ions (I\II) with PrP under physiological conditions (like pH ~ 7.4), enabling researchers to study the role played by copper and other ions in the progress of the prion disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
