ABSTRACT
Our observations on IDPs are dominated by in vitro experiments, and it is implicitly assumed that the emerging picture is relevant with respect to their state and affairs in a living cell. The cell, however, has extremely high intracellular macromolecular concentrations that give rise to a crowding effect, which might bear direct relevance on the structural state of IDPs (Ellis 2001; Minton 2005). Typical concentrations of proteins and other macromolecules reach 300-400 mg/ml, which basically limits the available space for other macromolecules (Figure 8.1) and causes a severe excluded volume effect that increases chemical activity of the molecules. Theoretical and experimental estimates suggest that this effect can be of several orders of magnitude for a protein of average size, which may fundamentally affect structural transitions accompanied by changes in volume, such as protein-protein interactions and folding. In the case of unfolded/denatured globular proteins, crowding does promote their native-like compact states of at least partial activity (Baskakov and Bolen 1998; McPhie, Ni, and
Minton 2006; Qu and Bolen 2002). By analogy, crowding may also force IDPs to assume compact or even folded states, making this issue very critical with respect to their physiological structural state and function.
