This title appears in the Scientific Report :
2013
Please use the identifier:
http://dx.doi.org/10.1080/07391102.2012.712477 in citations.
Dominant-negative effects in prion diseases: insights from molecular dynamics simulations on mouse prion protein chimeras
Dominant-negative effects in prion diseases: insights from molecular dynamics simulations on mouse prion protein chimeras
Mutations in the prion protein (PrP) can cause spontaneous prion diseases in humans (Hu) and animals. In transgenic mice, mutations can determine the susceptibility to the infection of different prion strains. Some of these mutations also show a dominant-negative effect, thus halting the replication...
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Personal Name(s): | Cong, Xiaojing |
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Bongarzone, Salvatore / Giachin, Gabriele / Rossetti, Giulia (Corresponding author) / Carloni, Paolo / Legname, Giuseppe | |
Contributing Institute: |
Jülich Supercomputing Center; JSC Computational Biomedicine; IAS-5 |
Published in: | Journal of biomolecular structure & dynamics: JBSD, 31 8, S. 829-840 |
Imprint: |
Abingdon, Oxon
Taylor & Francis
2013
|
DOI: |
10.1080/07391102.2012.712477 |
PubMed ID: |
22934595 |
Document Type: |
Journal Article |
Research Program: |
Computational Science and Mathematical Methods |
Publikationsportal JuSER |
Mutations in the prion protein (PrP) can cause spontaneous prion diseases in humans (Hu) and animals. In transgenic mice, mutations can determine the susceptibility to the infection of different prion strains. Some of these mutations also show a dominant-negative effect, thus halting the replication process by which wild type mouse (Mo) PrP is converted into Mo scrapie. Using all-atom molecular dynamics (MD) simulations, here we studied the structure of HuPrP, MoPrP, 10 Hu/MoPrP chimeras, and 1 Mo/sheepPrP chimera in explicit solvent. Overall, 2 μs of MD were collected. Our findings suggest that the interactions between α1 helix and N-terminal of α3 helix are critical in prion propagation, whereas the β2–α2 loop conformation plays a role in the dominant-negative effect. |