Аннотация:The pathogenesis of the various prion diseases is based on the conformational conversion of the prion proteinfrom its physiological cellular form to the insoluble scrapie isoform. Several chaperones, including the Hsp60family of group I chaperonins, are known to contribute to this transformation, but data on their effects are scarceand conflicting. In this work, two GroEL-like phage chaperonins, the single-ring OBP and the double-ring EL,were found to stimulate monomeric prion protein fbrillation in an ATP-dependent manner. The resulting fbrilswere characterised by thioflavin T fluorescence, electron microscopy, proteinase K digestion assay and othermethods. In the presence of ATP, chaperonins were found to promote the conversion of prion protein monomersinto short amyloid fbrils with their further aggregation into less toxic large clusters. Fibrils generated with theassistance of phage chaperonins differ in morphology and properties from those formed spontaneously frommonomeric prion in the presence of denaturants at acidic pH.
