Taurine Induces an Ordered but Functionally Inactive Conformation in Intrinsically Disordered Casein Proteins

Intrinsically disordered proteins (IDPs) are involved in various important biological processes, such as cell signalling, transcription, translation, cell division regulation etc. Many IDPs need to maintain their disordered conformation for proper function. Osmolytes, natural organic compounds responsible for maintaining osmoregulation, have been believed to regulate the functional activity of macromolecules including globular proteins and IDPs due to their ability of modulating the macromolecular structure, conformational stability, and functional integrity. In the present study, we have investigated the effect of all classes of osmolytes on two model IDPs, α- and β-casein. It was observed that osmolytes can serve either as folding inducers or folding evaders. Folding evaders, in general, do not induce IDP folding and therefore had no significant effect on structural and functional integrity of IDPs. On the other hand, osmolytes taurine and TMAO serve as folding inducers by promoting structural collapse of IDPs that eventually leads to altered structural and functional integrity of IDPs. This study sheds light on the osmolyte-induced regulation of IDPs and their possible role in various disease pathologies.