The Effect of Chemical Chaperones on Proteins with Different Aggregation Kinetics

Formation and accumulation of protein aggregates adversely affect intracellular processes in living cells and are negative factors in the production and storage of protein preparations. Chemical chaperones can prevent protein aggregation, but this effect is not universal and depends on the target protein structure and kinetics of its aggregation. We studied the effect of betaine (Bet) and lysine (Lys) on thermal aggregation of muscle glycogen phosphorylase b (Phb) at 48 degrees C (aggregation order, n = 0.5), UV-irradiated Phb (UV-Phb) at 37 degrees C (n = 1), and apo-form of Phb (apo-Phb) at 37 degrees C (n = 2). Using dynamic light scattering, differential scanning calorimetry, and analytical ultracentrifugation, we have shown that Bet protected Phb and apo-Phb from aggregation, but accelerated the aggregation of UV-Phb. At the same time, Lys prevented UV-Phb and apo-Phb aggregation, but increased the rate of Phb aggregation. The mechanisms of chemical chaperone action on the tertiary and quaternary structures and kinetics of thermal aggregation of the target proteins are discussed. Comparison of the effects of chemical chaperones on the proteins with different aggregation kinetics provides more complete information on the mechanism of their action.

Automated summary

Formation and accumulation of protein aggregates negatively impact cellular processes and protein preparations. The effectiveness of chemical chaperones in preventing protein aggregation depends on the structure and kinetics of the target protein. Betaine (Bet) protected Phb and apo-Phb from aggregation, but accelerated the aggregation of UV-Phb. Lysine (Lys) prevented UV-Phb and apo-Phb aggregation, but increased the rate of Phb aggregation. The study provides insights into the mechanisms of chemical chaperone action on protein structure and aggregation kinetics.