Naslov
Analysis of molecular mobility in pathogenic and protective mutants of human prion protein from 15N relaxation data

Autori
Zhukov, Igor ; Biljan, Ivana ; Giachin, Gabriele ; Ilc, Gregor ; Jurga, Stefan ; Plavec, Janez ; Legname, Guiseppe

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

Izvornik
Magnetic Moments in Central Europe 2015 Book of Abstracts / Kosiński, Krzysztof ; Urbańczyk, Mateusz ; Żerko, Szymon - Varšava : Nobell Congressing sp. z o.o., 2015, 85-85

Skup
Magnetic Moments in Central Europe 2015

Mjesto i datum
Krynica-Zdrój, Poljska, 25.02.2015. - 01.03.2015

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
prion protrein; mutants; NMR; backbone dynamics; 15N relaxation

Sažetak
Prion diseases, also known as transmissible spongiform encephalopathies (TSE), are a group of neuropathies characterized by a fatal spongiform neurodegeneration of the brain, facilitated by conformational changes in the prion protein (PrP) observed in humans and other animals. However, the initiation and propagation mechanisms by which PrP convert from normal cellular form (PrPC) to the protease resistant PrPSc form is still not understood in detail. One of the important factors of this phenomenon are processes of molecular dynamics which facilitate and control the conversion of PrPC to PrPSc forms. In the presented study, the backbone dynamics of the human pathogenic mutant (Q212P), protective mutant (Q218K), and two wild-type constructs PrP(90-231) and PrP(23-231) were analyzed at pH 5.5. The high resolution 3D structures of all mutants were solved previously in our group with the exception of the PrP(23-231) protein. There were several studies focused on analysis of 15N relaxation data performed on mouse PrP protein demonstrated similarity of dynamic performed on the mouse wild-type and several PrP mutants. Our studies focused on human pathological and protective PrP mutants. Experimental data (15N R1, R2 relaxation rates, and 1H-15N NOE) were acquired under two magnetic fields (16.4 T and 18.8 T) and analyzed with both Spectral Density Mapping and ModelFree formalisms. Moreover, results evaluated for the PrP(90-231) construct are analyzed together with whole length PrP(23-231) protein, which provide possibilities to explore tiny changes in dynamic processes caused by a long, unstructured N-terminal domain. Our studies reveal the possibility to explore the effects of molecular dynamics in the initial steps of the transformation of cellular PrPC into the pathogenic PrPSc form.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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