CEO, Kinepict Ltd, Budapest, Hungary
Associate Professor, Semmelweis University, Budapest, Hungary
The first experimental demonstration that a protein transformed into amyloids in a controlled way in vitro can be recovered from amyloids into the biologically active structure.
Amyloid deposits accumulated in numerous diseases are the final stage of multi-step protein conformational-conversion and oligomerization processes. The underlying molecular mechanisms are not fully understood, and particularly little is known about the reverse reaction. Here we show that amyloid fibrils formed of phosphoglycerate kinase (PGK) can be converted back into native protein. A recovery with 60 % efficiency was achieved, which is comparable to the success rate of the unfolding-refolding studies and the recovered enzyme was folded, stable and fully active. The key intermediate stages in the recovery process are fibril disassembly and unfolding followed by spontaneous protein folding.
Agócs G, Solymosi K, Varga A, Módos K, Kellermayer M, Závodszky P, Fidy J, Osváth S (2010)
FEBS Letters 584, 1139-1142, Recovery of functional enzyme from amyloid fibrils.