Pregled bibliografske jedinice broj: 696624
NMR insights into structural differences of cellular prion protein caused by mutations in human genome
NMR insights into structural differences of cellular prion protein caused by mutations in human genome // 4tʰ Annual Bio-NMR User Meeting Book of Abstracts / Kosiński, Krzysztof (ur.).
Varšava: Acclaim Studio Paweł Buchaniec, 2014. str. 87-87 (poster, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 696624 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
NMR insights into structural differences of cellular prion protein caused by mutations in human genome
Autori
Ilc, Gregor ; Biljan, Ivana ; Giachin, Gabriele ; Legname, Giuseppe ; Plavec, Janez
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
4tʰ Annual Bio-NMR User Meeting Book of Abstracts
/ Kosiński, Krzysztof - Varšava : Acclaim Studio Paweł Buchaniec, 2014, 87-87
ISBN
978-83-63311-90-2
Skup
4th Annual User group Meeting of Bio-NMR
Mjesto i datum
Varšava, Poljska, 05.05.2014. - 08.05.2014
Vrsta sudjelovanja
Poster
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Prion protein; Mutants; NMR spectroscopy
Sažetak
The development of transmissible spongiphorm encephalopathies (TSE) is associated with the conversion of the cellular prion protein (PrPC) into the misfolded, pathogenic isoform (PrPSc). In human genetic forms of these diseases, mutations in the globular C-terminal domain of PrPC are hypothesized to favor spontaneous generation of PrPSc in specific brain regions, leading to neuronal cell degeneration and death. Approximately 10–15% of TSEs are associated with the mutations. Our recent NMR studies were focused on structural characterization of different truncated recombinant human (Hu) 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 protect 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 with the structure of the WT Hu-PrP revealed that although structures share a similar global fold, mutations introduce some local structural differences. The determined 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
