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. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:4 . This is an Accepted Manuscript of an article published by Taylor & Francis in Journal of Biomolecular Structure and Dynamics on 2013, available online: http://www.tandfonline.com/10.1080/07391102.2012.712477.
|Titolo:||Dominant-negative effects in prion diseases: insights from molecular dynamics simulations on mouse prion protein chimeras|
|Autori:||Cong, X; Bongarzone, S; Giachin, G; Rossetti, G; Carloni, P; Legname, G|
|Rivista:||JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.1080/07391102.2012.712477|
|Appare nelle tipologie:||1.1 Journal article|