TY  - JOUR
AU  - Cong, Xiaojing
AU  - Bongarzone, Salvatore
AU  - Giachin, Gabriele
AU  - Rossetti, Giulia
AU  - Carloni, Paolo
AU  - Legname, Giuseppe
TI  - Dominant-negative effects in prion diseases: insights from molecular dynamics simulations on mouse prion protein chimeras
JO  - Journal of biomolecular structure & dynamics: JBSD
VL  - 31
IS  - 8
CY  - Abingdon, Oxon
PB  - Taylor & Francis
M1  - FZJ-2012-00920
SP  - 829-840
PY  - 2013
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000321732100003
C6  - pmid:22934595
DO  - DOI:10.1080/07391102.2012.712477
UR  - https://juser.fz-juelich.de/record/128024
ER  -