Contact-induced structure transformation in transmembrane prion propagation.
Based on recent experimental evidences of the transmission of prion diseases due to a particular transmembrane form (termed (Ctm)PrP), we propose a theoretical model for the molecular mechanism of such conformational diseases, in which a misfolded (Ctm)PrP induces a similar misfolding of another (Ctm)PrP. Computer simulations are performed to investigate the correlation between folding time and the concentration of misfolded PrP in various processes, including dimerization, trimerization, and cooperative dimerization. By comparing with the experimental correlation curve between incubation time and injected dose of scrapie prions, we conclude that cooperative dimerization may play an important role in the pathological mechanism of prion diseases.
Ou
D-M
DM
Department of Physics, National Taiwan Normal University, Taipei, Taiwan.
Chen
C-C
CC
Chen
C-M
CM
D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011328:Prions / Q000737:chemistry* / Q000648:ultrastructure*; D011485:Protein Binding; D011487:Protein Conformation
D046912:Multiprotein Complexes; D011328:Prions