Bacteriophage-encoded chaperonins stimulate prion protein fibrillation in an ATP-dependent manner

• Published in: Biochimica et biophysica acta. Proteins and proteomics 2024-01, Vol.1872 (1), p.140965-140965, Article 140965
• Main Authors: Leisi, Evgeniia V., Moiseenko, Andrey V., Kudryavtseva, Sofia S., Pozdyshev, Denis V., Muronetz, Vladimir I., Kurochkina, Lidia P.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Amyloid transformation; Animals; Bacteriophages - metabolism; Chaperonin 60 - chemistry; Phage chaperonin; Prion protein; Prion Proteins - chemistry; Prions - chemistry; Protein aggregation
• ISSN: 1570-9639; 1878-1454
• DOI: 10.1016/j.bbapap.2023.140965

The pathogenesis of the various prion diseases is based on the conformational conversion of the prion protein from its physiological cellular form to the insoluble scrapie isoform. Several chaperones, including the Hsp60 family of group I chaperonins, are known to contribute to this transformation, but data on their effects are scarce and 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 fibrillation in an ATP-dependent manner. The resulting fibrils were characterised by thioflavin T fluorescence, electron microscopy, proteinase K digestion assay and other methods. In the presence of ATP, chaperonins were found to promote the conversion of prion protein monomers into short amyloid fibrils with their further aggregation into less toxic large clusters. Fibrils generated with the assistance of phage chaperonins differ in morphology and properties from those formed spontaneously from monomeric prion in the presence of denaturants at acidic pH. [Display omitted] •ATP-dependent action of phage chaperonins stimulates prion protein amyloid conversion.•Short fibers induced by action of phage chaperonins aggregate to form large clusters.•Induced fibrils differ in morphology and properties from spontaneously formed fibrils.