Polymer effects modulate binding affinities in disordered proteins

Area of Science:

• Biochemistry
• Structural Biology
• Systems Biology

Background:

• Intrinsically disordered proteins (IDPs) are crucial in regulatory networks but sensitive to environmental changes.
• The impact of solution conditions on IDP folding-binding coupling remains unclear.

Purpose of the Study:

• Investigate how salt concentration influences the polymer properties and binding affinities of disordered proteins.
• Determine the functional relevance of disordered protein states in fluctuating cellular environments.

Main Methods:

• Single-molecule Förster resonance energy transfer (smFRET) experiments.
• Theoretical polymer physics modeling.
• All-atom molecular dynamics simulations.

Main Results:

• Increasing ionic strength causes surveyed disordered proteins to expand due to Debye-Hückel charge screening.
• Pairwise protein affinities increase significantly (order of magnitude) within physiological salt ranges.
• Changes in the disordered state account for 50% of the observed binding affinity enhancement.

Conclusions:

• Disordered protein states possess functional relevance, impacting binding affinities.
• Networks of homologous disordered proteins exhibit robustness in variable cellular environments.
• Understanding IDP sensitivity to ionic strength is key for predicting network behavior.