Driving forces of the complex formation between highly charged disordered proteins.

Area of Science:

• Biochemistry
• Biophysics
• Molecular Biology

Background:

• Intrinsically disordered proteins (IDPs) form highly disordered complexes.
• Oppositely charged IDPs represent a novel class of biomolecular interactions.

Purpose of the Study:

• Investigate the thermodynamic driving forces behind interactions between intrinsically disordered proteins.
• Characterize the binding of histone H1 (H1) and prothymosin α (ProTα).

Main Methods:

• Temperature-dependent single-molecule Förster resonance energy transfer (smFRET).
• Isothermal titration calorimetry (ITC).
• Salt-dependent affinity measurements.
• Mean-field polyelectrolyte theory.

Main Results:

• ProTα-H1 binding is enthalpically unfavorable.
• Counterion release entropy is a key thermodynamic driver.
• Ternary complexes of ProTα and H1 exist alongside heterodimers.
• Observed thermodynamics are quantitatively explained by polyelectrolyte theory.

Conclusions:

• Counterion release is crucial for charged biomolecular interactions.
• ProTα-H1 complex formation principles apply broadly to charged biomolecules.
• IDP complex formation shares similarities with synthetic polyelectrolyte interactions.