Effect of Trehalose on Oligomeric State and Anti-Aggregation Activity of αB-Crystallin

alpha B-Crystallin (alpha B-Cr), one of the main crystalline lens proteins, along with other crystallins maintains lens transparency suppressing protein aggregation and thus preventing cataractogenesis. alpha B-Cr belongs to the class of molecular chaperones; being expressed in many tissues it has a dynamic quaternary structure, which is essential for its chaperone-like activity. Shift in the equilibrium between ensembles of oligomers of different size allows regulating the chaperone activity. Trehalose is known to inhibit protein aggregation in vivo and in vitro, and it is widely used in biotechnology. The results of studying the effect of trehalose on the chaperone-like activity of crystallins can serve as a basis for the design of drugs delaying cataractogenesis. We have studied the trehalose effect on the quaternary structure and anti-aggregation activity of alpha B-Cr using muscle glycogen phosphorylase b (Phb) as a target protein. According to the dynamic light scattering data, trehalose affects the nucleation stage of Phb thermal aggregation at 48 degrees C, and an increase in the alpha B-Cr adsorption capacity (AC(0)) is the main effect of trehalose on the aggregation process in the presence of the protein chaperone (AC(0) increases 1.5-fold in the presence of 66 mM trehalose). According to the sedimentation analysis data, trehalose stabilizes the dimeric form of Phb at the stages of denaturation and dissociation and enhances the interaction of alpha B-Cr with the target protein. Moreover, trehalose shifts the equilibrium between the alpha B-Cr oligomers towards the smaller forms. Thus, trehalose affects the quaternary structure of alpha B-Cr and increases its anti-aggregation activity at the nucleation stage.

Automated summary

This study investigated the effect of trehalose on the quaternary structure and anti-aggregation activity of alpha B-Cr. The results showed that trehalose affected the nucleation stage of Phb thermal aggregation and increased the adsorption capacity of alpha B-Cr during the aggregation process. Additionally, trehalose stabilized the dimeric form of Phb and enhanced the interaction between alpha B-Cr and the target protein.