Effects of confinement on structure and dynamics of IDPs

IDPs are present in all in sub-cellular compartments. As total protein concentrations for the eukaryotic cytoplasm and the nucleus are estimated to be between 100 to 400 mg/ml, IDPs need to maintain their function in highly confined macromolecular environments with restricted molecular motion and multiple intermolecular interactions. However, for synthetic macromolecules, conditions of macromolecular crowding lead to a collapse from the Gaussian chain conformation (𝑅𝑅~𝑀𝑀1/2) to a compact globule (𝑅𝑅~𝑀𝑀1/3)39, and it has been predicted that the conformational space of IPDs will be strongly affected by molecular crowding. While this behavior was observed for artificially unfolded proteins, globular proteins are also strongly influenced 40. Experiments with natural IDPs reveal an ambiguous picture. For example, it is still under debate what properties of the crowders and the IDPs stabilize the disordered state, leading either to structure formation or collapse of structures. A comparative study using different IDPs and crowders will help to disentangle enthalpic contributions, e.g. electrostatic interactions, and entropic contributions, e.g. excluded volume effects. These investigations will contribute to a deeper understanding of the impact of macromolecular confinement on the structure and function of IDPs.