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

蛋白质折叠和寡聚化程度如何调节凝聚体的形成和性质

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Abstract

Although proteins across the order-disorder continuum can undergo phase separation, it remains unclear how the structural states of the protein constituents influence the material properties of the resulting condensates. Here, using a coarse-grained model of a primordial peptide-RNA system, we investigate how condensates formed from ordered versus disordered peptides differ in their properties. By systematically varying the degree of foldedness and oligomerization of the peptide constituents, we find that stronger peptide-peptide interactions reduce diffusivity, whereas stronger peptide-RNA interactions destabilize the condensate. We further show that peptide conformational plasticity modulates the balance between these interactions, acting as a powerful lever for tuning the condensate properties. This work highlights how subtle changes in protein structure shape condensate architecture, dynamics, or stability and, together with experimental observations, provides a framework for understanding how the evolutionary shift from disordered to ordered peptides may have expanded the material repertoire of biomolecular condensates.

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