Salt-Dependent Conformational Changes of Intrinsically Disordered Proteins

The flexible structure of an intrinsically disordered protein (IDP) is known to be perturbed by salt concentrations, which can be understood by electrostatic screening on charged amino acids. However, an IDP usually contains more uncharged residues that are influenced by the salting-out effect. Here we have parametrized the salting-out effect into a coarse-grained model using a set of Forster resonance energy transfer data and verified with experimental salt-dependent liquid-liquid phase separation (LLPS) of 17 proteins. The new model can correctly capture the behavior of 6 more sequences, resulting in a total of 13 when varying salt concentrations. Together with a survey of more than 500 IDP sequences, we conclude that the salting-out effect, which was considered to be secondary to electrostatic screening, is important for IDP sequences with moderately charged residues at physiological salt concentrations. The presented scheme is generally applicable to other computational models for capturing salt-dependent IDP conformations.

Automated summary

The study introduced a new model to explain the influence of salt on protein structure, revealing the significant role of salting-out effect in IDP sequences, especially those with moderately charged residues. This model also shows general applicability in conformation studies of other proteins.