Pregled bibliografske jedinice broj: 612375
NMR insights into links that correlate structural features with onset of prion diseases
NMR insights into links that correlate structural features with onset of prion diseases // XXVth International Conference on Magnetic Resonance in Biological Systems
Lyon, Francuska, 2012. str. 237-237 (poster, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 612375 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
NMR insights into links that correlate structural features with onset of prion diseases
Autori
Ilc, Gregor ; Biljan, Ivana ; Giachin, Gabriele, Zhukov, Igor ; Legname, Giuseppe ; Plavec, Janez
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
XXVth International Conference on Magnetic Resonance in Biological Systems
/ - , 2012, 237-237
Skup
XXVth International Conference on Magnetic Resonance in Biological Systems
Mjesto i datum
Lyon, Francuska, 19.08.2012. - 24.08.2012
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
NMR ; Structure ; Prions ; Mutants
Sažetak
Prion diseases or Transmissible Spongiform Encephalopathies (TSEs) are a group of fatal neurodegenerative illnesses affecting humans and animals. They are classified into sporadic, genetic and infectious forms. Genetic prion diseases are caused by mutations in the human prion protein gene and include Gerstmann-Sträussler-Scheinker (GSS) syndrome, Fatal Familial Insomnia and genetic Creutzfeldt–Jakob disease (CJD). Approximately 10-15% of all TSE cases in humans are associated with mutations. The development of TSEs is associated with the conversion of the cellular prion protein (PrPC) into a misfolded, pathogenic isoform (PrPSc). In our recent works, we have determined the NMR solution-state structures of the truncated recombinant human (Hu) PrPs carrying the pathological Q212P (90-231, M129) and V210I (90-231, M129) mutations. While Q212P mutation is linked to GSS the V210I mutation is linked to genetic CJD. The determined structures of both mutants consist of unstructured N-terminal part (residues 90-124) and well-defined C-terminal domain (residues 125-228). Analysis and comparison with the structure of the WT HuPrP revealed that although structures share similar global fold, mutations introduces some local structural differences. The observed variations are mostly clustered at the α2-α3 inter-helical interface and in the β2-α2 loop region. NMR structures offer new clues on the earliest events of the pathogenic conversion process and could be used for the development of antiprion drugs.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
