Modeling of a propagation mechanism of infectious prion protein; a hexamer as the minimum infectious unit.
To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrP(Sc)), here we conducted a disruption simulation of a PrP(Sc) nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrP(Sc) model structure. The simulation results showed that the nonamer disrupted in cooperative manners into monomers via two significant intermediate states: (1) a nonamer with a partially unfolded surface trimer and (2) a hexamer and three monomers. Dimers and trimers were rarely observed. Then, we propose a new PrP(Sc) propagation mechanism where a hexamer plays an essential role as a minimum infectious unit.
Division of Prion Research, Center for Emerging Infectious Diseases, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Hironori K
HK
Nakamura
Mitsunori
M
Takano
Kazuo
K
Kuwata
D003198:Computer Simulation; D008954:Models, Biological; D008958:Models, Molecular; D018620:PrPSc Proteins / Q000737:chemistry*; D011328:Prions; D011487:Protein Conformation; D017510:Protein Folding; D013816:Thermodynamics
D018620:PrPSc Proteins; D011328:Prions