Naslov
NMR structural studies of human cellular prion proteins with disease linked point mutations

Autori
Ilc, Gregor ; Biljan, Ivana ; Plavec, janez

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Trends in biomolecular structure: from chemistry to function: programme and book of abstracts / Zavasnik, J. - Ljubljana, 2013, 31-31

ISBN
978-961-281-158-7

Skup
Trends in biomolecular structure: from chemistry to function

Mjesto i datum
Ljubljana, Slovenija, 03.10.2013. - 05.10.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Prion protein; Genetic mutations; Polymorphisms; Prion diseases; 3D structure; NMR spectroscopy

Sažetak
Prion diseases or transmissible spongiform encephalopathies are fatal neurodegenerative disorders associated with the conformational conversion of the cellular prion protein, PrPC, into a pathological form known as prion of PrPSc. They can be classified into sporadic, inherited and infectious forms. Spontaneous generation of PrPSc in inherited forms of prion diseases is caused by mutations in the human prion protein gene. A major goal in prion biology is unravelling the molecular mechanism by which PrPC misfolds and leads to development of diseases. Structural characterization of various human PrP (HuPrP) variants may be helpful for better understanding of the earliest stages of the conformational changes leading to spontaneous generation of prions. Our recent NMR studies were focused on structural characterization of different truncated recombinant human PrPs carrying the pathological Q212P (90-231, M129), V210I (90-231, M129) mutations and protective E219K (90-231, M129) polymorphism. While Q212P mutation is linked to GSS the V210I mutation is linked to genetic CJD. The naturally occurring E219K polymorphism in the HuPrP is considered to be protective against sCJD. We have demonstrated that the determined structures of variants consist of unstructured N-terminal part (residues 90-124) and well-defined C-terminal domain (residues 125-228). Analysis and comparison of determined structures with respect to the structure of the WT Hu-PrP revealed that although structures share similar global fold, mutations introduce local structural differences. The determined NMR structures offer new clues on the earliest events of the pathogenic conversion process, which is particularly interesting for the development of antiprion drugs.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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