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Allostery in Biomolecular Condensates.

Ruth Nussinov1, Clil Regev2, Hyunbum Jang3

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Allosteric regulation, crucial for protein function, is enhanced within biomolecular condensates due to increased protein interactions. Condensate concentration, influenced by cell state, determines the effectiveness of this allosteric signaling.

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Area of Science:

  • Biophysics
  • Cell Biology
  • Molecular Biology

Background:

  • Allosteric proteins and membrane-less biomolecular condensates are key cellular components governed by physical principles.
  • Allosteric regulation is an intrinsic property of dynamic proteins, essential for cellular processes.
  • Biomolecular condensates provide unique environments that can facilitate and modulate allosteric effects.

Purpose of the Study:

  • To explore the role and effectiveness of allosteric regulation within biomolecular condensates.
  • To investigate how the condensate environment influences protein interactions and allosteric signaling.
  • To determine the impact of cellular state and concentration on allosteric function in condensates.

Main Methods:

  • Theoretical analysis of protein dynamics and interactions within condensed phases.
  • Examination of the physical properties of biomolecular condensates, including water content and protein concentration.
  • Correlation of cellular states (e.g., proliferation, senescence) with condensate characteristics and allosteric potential.

Main Results:

  • The condensate environment, characterized by high protein concentration and specific interactions, promotes allosteric regulation.
  • Hydrophobic interactions and multivalent networks are critical for signal transmission within condensates.
  • Dilution, determined by cell state, is a key factor controlling the efficacy of allosteric mechanisms in condensates.

Conclusions:

  • Effective allosteric signaling within biomolecular condensates is dependent on the cell's physiological state and the resulting condensate concentration.
  • Condensates can enhance allostery under normal conditions but may become dysfunctional if too dilute or too concentrated.
  • Allosteric regulation in condensates is integral to cellular signaling, connecting receptors to the cytoskeleton.