Pregled bibliografske jedinice broj: 694966
Insights into molecular structures of human prion proteins with inherited mutations by NMR
Insights into molecular structures of human prion proteins with inherited mutations by NMR // SNC'13 Book of Abstracts / Judita Jeran, Blaž Koritnik (ur.).
Ljubljana: Slovenian Neuroscience Association (SiNAPSA), 2013. str. 43-43 (predavanje, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 694966 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
Insights into molecular structures of human prion proteins with inherited mutations by NMR
Autori
Ilc, Gregor ; Giachin, Gabriele ; Biljan, Ivana ; Legname, Giuseppe ; Plavec, Janez
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
SNC'13 Book of Abstracts
/ Judita Jeran, Blaž Koritnik - Ljubljana : Slovenian Neuroscience Association (SiNAPSA), 2013, 43-43
ISBN
978-961-91704-5-8
Skup
SiNAPSA Neuroscience Conference '13 (SNC'13)
Mjesto i datum
Ljubljana, Slovenija, 27.09.2013. - 29.09.2013
Vrsta sudjelovanja
Predavanje
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Prion protein; Mutants; NMR spectroscopy; pH
Sažetak
Understanding mechanisms by which cellular prion protein (PrPC) misfolds and leads to disease may benefit from detailed analysis of 3D structures. Our recent studies utilizing heteronuclear Nuclear Magnetic Resonance spectroscopy in solution have focused on structural characterization of different human PrPC variants that are linked to genetic prion diseases. High-resolution structures of Q212P, V210I and E219K mutants exhibit unique structural features that are caused by a single amino acid substitution and suggest molecular mechanisms of early events of the conformational conversion of PrPC to its pathological form, PrPSc. Structural details of human prion protein HuPrP(90-231) carrying V210I mutation were analyzed under acidic and neutral pH conditions. While nearly complete assignment was obtained for V210I mutant at pH 5.5, amide protons are involved in fast exchange with solvent at pH 7.2 which renders observation of some amino acids residues from unstructured N-terminal region. Significant pH-related local structural differences were observed in the α2−α3 interhelical region, at the interface of the β1−α1 loop, in helices α1 and α3, and in the β2−α2 loop region. The detailed analysis of interactions suggests that spontaneous misfolding of PrPC may occur under acidic-pH conditions in endosomal compartments.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
