Pregled bibliografske jedinice broj: 616002
NMR structure of the human prion protein with the pathological Q212P mutation: insights into inherited human prion diseases
NMR structure of the human prion protein with the pathological Q212P mutation: insights into inherited human prion diseases // Bio-NMR and EAST-NMR Annual User Meeting
Brno, Češka Republika, 2011. str. 41-41 (predavanje, međunarodna recenzija, sažetak, znanstveni)
CROSBI ID: 616002 Za ispravke kontaktirajte CROSBI podršku putem web obrasca
Naslov
NMR structure of the human prion protein with the pathological Q212P mutation: insights into inherited human prion diseases
Autori
Giachin, Gabriele ; Ilc, Gregor ; Biljan, Ivana ; Jaremko, Mariusz ; Jaremko, Lukasz ; Benetti, Federico ; Plavec, Janez ; Zhukov, Igor ; Legname, Giuseppe
Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni
Izvornik
Bio-NMR and EAST-NMR Annual User Meeting
/ - , 2011, 41-41
Skup
Bio-NMR and EAST-NMR Annual User Meeting
Mjesto i datum
Brno, Češka Republika, 24.01.2011. - 27.01.2011
Vrsta sudjelovanja
Predavanje
Vrsta recenzije
Međunarodna recenzija
Ključne riječi
Prions ; NMR ; Mutants
Sažetak
Prion diseases are a group of neuropathies characterized by a spongiform neurodegeneration of the brain caused by prions. According to the "protein-only hypothesis", during prion diseases the cellular prion protein, PrPC, is converted into an abnormal form, called PrPSc, by a not well-elucidated process of conversion from the alpha-helix into beta -sheet secondary structures. One of the strongest arguments supporting the "protein only hypothesis" is the link between prion diseases and inherited human mutations in the PRNP gene. Several point mutations leading to familial Creutzfeldt-Jakob (CJD) disease, Gerstmann-Straussler-Scheinker (GSS) disease, Fatal Familial Insomnia have been identifi ed in PRNP gene. Our understanding of the mechanisms by which mutations cause disease remains limited. We believe that high-resolution 3D structure of the mutated prion protein, more susceptible for spontaneous conversion into the infectious form, will help us to understand the molecular mechanism at early stages of the disease. In this study we determined and examined a high-resolution 3D structure of the truncated recombinant human PrP (residue from 90 to 231) containing the GSS-related Q212P mutation. The substitution of a glutamine by a proline at the position 212 reveals novel structural differences in comparison to the known PrP structures. The most remarkable differences involve the C-terminal end of the protein and the beta2-alpha2 loop region. This structure might provide new insights into the early events of conformational transition of PrPC into PrPSc. Indeed, the spontaneous formation of prions in familial cases might be due to the disruptions of the hydrophobic core consisting of beta2-alpha2 loop and alpha3 helix.
Izvorni jezik
Engleski
Znanstvena područja
Kemija
