Depletion interactions modulate the binding between disordered proteins in crowded environments

• DOI: 10.1073/pnas.1921617117
• Publication Date: 2020-06-02T20:06:47Z
• Authors: Franziska Zosel; Andrea Soranno; Karin J. Buholzer; Daniel Nettels; Benjamin Schuler
• Keywords: 1000 Multidisciplinary; Protein Folding; 0303 health sciences; Macromolecular Substances; Protein Stability; Viscosity; 610 Medicine & health; 10192 Physics Institute; Biological Sciences; Single Molecule Imaging; Polyethylene Glycols; Intrinsically Disordered Proteins; Kinetics; 03 medical and health sciences; Models, Chemical; 10019 Department of Biochemistry; 570 Life sciences; biology; Protein Binding

Significance The molecular environment in a biological cell is much more crowded than the conditions commonly used in biochemical and biophysical experiments in vitro. It is therefore important to understand how the conformations and interactions of biological macromolecules are affected by such crowding. Addressing these questions quantitatively, however, has been challenging owing to a lack of sufficiently detailed experimental information and theoretical concepts suitable for describing crowding, especially when polymeric crowding agents and biomolecules are involved. Here, we use the combination of extensive single-molecule experiments with established and recent theoretical concepts to investigate the interaction between two intrinsically disordered proteins. We observe pronounced effects of crowding on their interactions and provide a quantitative framework for rationalizing these effects.