Polyanion order controls liquid-to-solid phase transition in peptide/nucleic acid co-assembly

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Membraneless organelles, such as ribonucleoprotein granules (RNPs), are crucial for cellular functions and involve RNA-protein interactions.
• The fused in sarcoma (FUS) protein, implicated in neurodegenerative diseases, undergoes phase separation influenced by adenosine triphosphate (ATP).

Purpose of the Study:

• To investigate RNA-templated ordering of the amyloid-beta (Aβ) peptide motif associated with Alzheimer's disease.
• To explore how structured phosphates influence the phase transition of Aβ peptide assemblies.

Main Methods:

• Studied the self-assembly of a cross-β propensity Aβ peptide motif.
• Examined the impact of various structured phosphates (DNA, trimetaphosphate) on Aβ peptide coacervate phase transitions.
• Analyzed the formation of supramolecular assemblies and paracrystalline structures.

Main Results:

• The Aβ peptide motif forms liquid-like coacervates that can be templated.
• Structured phosphates differentially affect the liquid-to-solid phase transition of Aβ assemblies.
• Phosphate structures influence the formation of paracrystalline assemblies.

Conclusions:

• Ordered environmental templates, such as structured phosphates, can guide the transition of Aβ peptides towards potentially pathogenic assemblies.
• Findings provide insights into the dynamics of ordering in polymer co-assemblies and the formation of pathological structures.