How the Extent of Protein Folding and Oligomerization Modulate Condensate Formation and Properties

Area of Science:

• Biophysics
• Molecular Biology
• Soft Matter Physics

Background:

• Proteins can transition between ordered and disordered states, influencing their ability to form biomolecular condensates.
• The material properties of these condensates are not fully understood in relation to the structural states of their protein components.

Purpose of the Study:

• To investigate how condensates formed from ordered versus disordered peptides differ in their material properties.
• To explore the role of peptide structure, interactions, and conformational plasticity in modulating condensate characteristics.

Main Methods:

• Utilized a coarse-grained computational model.
• Simulated a primordial peptide-RNA system.
• Systematically varied peptide foldedness and oligomerization.

Main Results:

• Stronger peptide-peptide interactions decreased condensate diffusivity.
• Stronger peptide-RNA interactions destabilized the condensate.
• Peptide conformational plasticity was identified as a key factor in tuning condensate properties.

Conclusions:

• Subtle changes in protein structure critically influence condensate architecture, dynamics, and stability.
• The study provides a framework for understanding how the evolution of protein structure impacts biomolecular condensate diversity.
• Findings bridge computational insights with experimental observations for a comprehensive view.