Denaturing Effect of Guanidine Hydrohloride on Amyloid Fibrils

Abstract

According to modern concepts, monomeric proteins under native conditions have a unique three-dimensional structure determined and optimized evolutionarily. This structure encoded by amino acid sequence that ensures the correct folding of protein molecules. Amyloid fibrils formed from the same protein under different conditions, on the contrary, can vary in their structure. Given the significant differences in the morphology of amyloid fibrils and monomeric proteins, it can be assumed that conformational stability of these states of the proteins also varies significantly. To revealing these differences denaturing effects can be used. In this work the depolymerization of amyloid fibrils formed from lysozyme and Abeta-peptide induced by denaturating agent guanidine hydrochloride was studied. Using the wide range of physicochemical approaches (including specially elaborated) we showed that amyloids are far from as stable as they are considered (even less stable than monomeric proteins). These results are a step towards identifying effects that can lead to degradation of amyloids and their clearance in vivo without adverse effects on the functionally active state of the proteins forming them. This work was supported by grant from Russian Science Foundation No 18-74-10100 (experiments with lysozyme) and RF President Fellowship SP-841.2018.4 (experiments with Abeta-peptide).