To construct a new model of the propagation mechanism of infectious scrapie-type prion protein (PrPsc), here we conducted a disruption simulation of a PrPsc nonamer using structure-based molecular dynamics simulation method based on a hypothetical PrPsc 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 PrPsc propagation mechanism where a hexamer plays an essential role as a minimum infectious unit. (c) 2007 Elsevier Inc. All rights reserved.