Molecules 2013, 18(8), 9451-9476; doi:10.3390/molecules18089451
Review

Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy

1email, 2email, 3,4email, 3,4,5email and 1,* email
Received: 27 June 2013; in revised form: 1 August 2013 / Accepted: 5 August 2013 / Published: 7 August 2013
(This article belongs to the Special Issue NMR of Proteins and Small Biomolecules)
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Abstract: The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs) and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process whereby most α-helical motifs are replaced by β-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal domain region of PrPC and cause spontaneous conversion to PrPSc. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify “hot spots” in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrPC epitopes thought to be involved in modulating prion susceptibility. Here we present a detailed overview of our solution-state NMR studies on human prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research.
Keywords: prion protein; prions; genetic mutations; polymorphisms; prion diseases; 3D structure; NMR spectroscopy
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Giachin, G.; Biljan, I.; Ilc, G.; Plavec, J.; Legname, G. Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy. Molecules 2013, 18, 9451-9476.

AMA Style

Giachin G, Biljan I, Ilc G, Plavec J, Legname G. Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy. Molecules. 2013; 18(8):9451-9476.

Chicago/Turabian Style

Giachin, Gabriele; Biljan, Ivana; Ilc, Gregor; Plavec, Janez; Legname, Giuseppe. 2013. "Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy." Molecules 18, no. 8: 9451-9476.


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