Trehalose promotes structural disorderness of intrinsically disordered casein proteins with enhanced chaperone function

Intrinsically disordered proteins (IDPs) are being currently explored for their role in wide range of essential cellular processes especially signalling, cell cycle, transcription, translation and several disease processes like neurodegeneration, cancer, systemic amyloidosis etc. However, as compared to ordered proteins, their high structural dynamics makes them quite sensitive to the changing cellular environment such as changes in the level of cellular metabolites. Since previous studies have shown the ability of trehalose (an important small molecule metabolite) to affect protein folding and formation of high order oligomers, we aim to elucidate the effect of trehalose on the structural-functional elasticity of intrinsically disordered & alpha;- and & beta;-casein proteins. We observed that trehalose enhances disorderliness resulting in increased chaperone activity of both the casein proteins. Considering the role of co-solutes in cellular proteostasis, the present study indicates that trehalose acts not only as an osmoprotectant, but also a key regulator of functional activity of various IDPs.