NR AHBS
AU Laurent,M.
TI Autocatalytic processes in cooperative mechanisms of prion diseases
QU FEBS Letters 1997 Apr 21; 407(1): 1-6
PT journal article
AB According to the leading theory, the agent responsible for prion diseases would be the conformational isomer PrPsc of a cellular protein PrPc, the pathogenic form PrPsc multiplying by converting the normal protein into a likeness of itself. The pathogenic isoform could catalyze the conformational transition so that the process, taken as a whole, is autocatalytic. However, in this simple but atypic model, unrealistic values of rate parameters are needed in order to account for the kinetics of the propagation of prion diseases. In this paper, I show that these limits can be overcome by assuming that catalysis proceeds through a multimeric assembly of the pathogenic isoform of the prion protein. Such a structure would indeed be able to provide cooperativity both at the assembly and conformational change levels, strongly reinforcing the autocatalytic character of the activated process. Moreover, such a property is a prerequisite to endow the metabolic system with dynamic bistability. Together with a good agreement regarding experimental data, this analysis is closely akin to Griffith's original idea concerning the thermodynamic conditions required for autocatalyzed modifications of any protein.
MH Allosteric Regulation; Animal; Catalysis; *Models, Chemical; PrPc Proteins/*metabolism; PrPsc Proteins/*metabolism; Prion Diseases/etiology/*metabolism; Protein Folding; Support, Non-U.S. Gov't; Thermodynamics
AD Service d'Imagerie Cellulaire, URA 1116 CNRS, Universite Paris-Sud, Centre d'Orsay, France.
SP englisch
PO Niederlande