Intrinsically disordered proteins and their environment: effects of strong denaturants, temperature, pH, counter ions, membranes, binding partners, osmolytes, and macromolecular crowding.

Intrinsically disordered proteins (IDPs) differ from "normal" ordered proteins at several levels, structural, functional and conformational. Amino acid biases characteristic for IDPs determine their structural variability and lack of rigid well-folded structure. This structural plasticity is necessary for the unique functional repertoire of IDPs, which is complementary to the catalytic activities of ordered proteins. Amino acid biases also drive atypical responses of IDPs to changes in their environment. The conformational behavior of IDPs is characterized by the low cooperativity (or the complete lack thereof) of the denaturant-induced unfolding, lack of the measurable excess heat absorption peak(s) characteristic for the melting of ordered proteins, "turned out" response to heat and changes in pH, the ability to gain structure in the presence of various counter ions, osmolytes, membranes and binding partners, and by the unique response to macromolecular crowding. This review describes some of the most characteristic features of the IDP conformational behavior and the unique response of IDPs to changes in their environment.