Prion-like low-complexity sequences: Key regulators of protein solubility and phase behavior

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Proteins with complex folding landscapes, like RNA-binding proteins, require cellular mechanisms for maintaining solubility and proper folding.
• Cellular strategies for managing protein folding, especially under stress, remain largely uncharacterized.

Purpose of the Study:

• To propose that prion-like low-complexity regions (LCRs) are critical regulators of protein solubility and folding.
• To re-evaluate the function of prion-like LCRs, moving beyond the concept of autonomous aggregation modules.

Main Methods:

• Literature review and synthesis of emerging evidence on prion-like LCRs.
• Analysis of protein sequences and their role in phase behavior and stress response.

Main Results:

• Prion-like LCRs function as protein-specific sequences with chaperone-like properties.
• Evidence suggests LCRs modulate protein phase behavior rather than solely forming amyloid-like structures.

Conclusions:

• Prion-like LCRs are key regulators of protein solubility and folding.
• These regions have evolved to manage protein phase transitions and confer protection against proteotoxic stress.