Only the reduced conformer of α-lactalbumin is inducible to aggregation by protein aggregates

Reduced apo-alpha -lactalbumin (r-LA) in the pre-molten globule state is soluble in neutral and reduced buffer at 25 degreesC but becomes aggregated when aggregates of various proteins are added. However, protein aggregates do not induce the aggregation of apo-or-lactalbumin in the molten globule state. The presence of the molecular chaperone protein disulfide isomerase or the "chemical chaperone" polyethyleneglycol inhibits the induced aggregation. Native proteins, aggregation-free folding intermediates, and soluble aggregates do not induce the aggregation. The interaction between r-LA and protein aggregates is hydrophobic in nature. These findings suggest that pre-molten globule state of LA is the target not only for chaperones but also for protein aggregates.