Prions and chaperones: Friends or foes?

Abstract

This review highlights the modern perception of anomalous folding of the prion protein and the role of chaperones therein. Special attention is paid to prion proteins from mammalian species, which are prone to amyloid-like prion diseases due to a unique aggregation pathway. Despite being a significantly popular current subject of investigations, the etiology, structure, and function of both normal and anomalous prion proteins still hold many mysteries. The most interesting of those are connected to the interaction with chaperone system, which is responsible for stabilizing protein structure and disrupting aggregates. In the case of prion proteins the following question is of the most importance - can chaperones influence different stages of the formation of pathological aggregates (these vary from intermediate oligomers to mature amyloid-like fibrils) and the whole transition from native prion protein to its amyloid-like fibril-enriched form? The existing inconsistencies and ambiguities in the observations made so far can be attributed to the fact that most of the investigations did not take into account the type and functional state of the chaperones. This review discusses in detail our previous works that have demonstrated fundamental differences between eukaryotic and prokaryotic chaperones in the action exerted on the amyloid-like transformation of the prion protein along with the dependence of the observed effects on the functional state of the chaperone.

Identification of Amyloidogenic Regions in Pseudomonas aeruginosa Ribosomal S1 Protein

“…The study of amyloids as ordered fibrillar protein aggregates is of great importance for elucidating their role in human pathologies, especially in neurodegenerative diseases [ 1 , 2 , 3 ]. It is known that, under certain conditions, most proteins and peptides tend not only to aggregation, but also to form amyloid-like fibrils [ 4 , 5 , 6 ]; in a particular case, the formation of amyloids of some proteins can be induced by other amyloidogenic proteins and peptides [ 7 , 8 ].…”