Protein Network Structure Enables Switching between Liquid and Gel States

Area of Science:

• Cellular Biology
• Biophysics
• Protein Biochemistry

Background:

• Biomolecular condensates are crucial for cellular organization, formed via phase separation.
• The encoding of material properties and phase specificity within constituent molecules remains poorly understood.

Purpose of the Study:

• To elucidate the phase behavior of the cancer-related protein SPOP and its substrate DAXX using analytical theory.
• To explain how competing molecular interactions govern the formation of distinct liquid and gel phases.

Main Methods:

• Analytical theory applied to binary mixtures of SPOP and DAXX.
• Analysis of phase diagrams including dilute liquid, dense liquid, and gel states.

Main Results:

• Phase separation is driven by a competition between SPOP-DAXX and DAXX-DAXX interactions.
• Gel formation is entropically driven by DAXX distribution on SPOP binding sites, not binding energy.
• Distinct phases arise from the interplay of interaction strengths and molecular concentrations.

Conclusions:

• The molecular architecture of phase-separating proteins dictates the structure, properties, and function of biomolecular condensates.
• Analytical theory provides a framework for understanding condensate properties at relevant biological scales.