Change in the Kinetic Regime of Aggregation of Yeast Alcohol Dehydrogenase in the Presence of 2-Hydroxypropyl-β-cyclodextrin

Chemical chaperones are low-molecular-weight compounds that suppress protein aggregation. They can influence different stages of the aggregation process-the stage of protein denaturation, the nucleation stage and the stage of aggregate growth-and this may lead to a change in the aggregation kinetic regime. Here, the possibility of changing the kinetic regime in the presence of a chemical chaperone 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) was investigated for a test system based on the thermally induced aggregation of yeast alcohol dehydrogenase (yADH) at 56(degrees)C. According to differential scanning calorimetry data, 2-HP-beta-CD did not affect the stage of the protein molecule unfolding. Dynamic light scattering data indicated changes in the aggregation kinetics of yADH during the nucleation and aggregate growth stages in the presence of the chaperone. The analysis of kinetic curves showed that the order of aggregation with respect to protein (n(c)), calculated for the stage of aggregate growth, changed from n(c) = 1 to n(c) = 2 with the addition of 100 mM 2-HP-beta-CD. The mechanism of 2-HP-beta-CD action on the yADH thermal aggregation leading to a change in its kinetic regime of aggregation is discussed.

Automated summary

Chemical chaperones are capable of suppressing protein aggregation at different stages. This study investigates the change in aggregation kinetics of yeast alcohol dehydrogenase in the presence of 2-hydroxypropyl-beta-cyclodextrin. The results show that the addition of the chaperone alters the aggregation kinetics and the order of aggregation with respect to protein.