Tuning Formation of Protein-DNA Coacervates by Sequence and Environment.

Area of Science:

• Biophysics
• Molecular Biology
• Biochemistry

Background:

• The cell nucleus contains high concentrations of nucleic acids and positively charged proteins.
• These components offer opportunities for complex coacervation, a liquid-liquid phase separation process.
• Histone proteins, particularly their C-termini, play a role in organizing nucleic acids.

Purpose of the Study:

• To investigate the formation and properties of coacervates formed by nucleic acids and the polycationic C-terminus of histone H1 (CH1).
• To understand how molecular properties like charge distribution influence phase separation and ordering.
• To explore the relationship between coacervate structure and molecular diffusion.

Main Methods:

• Utilized a minimal coarse-grained model to simulate mixtures of nucleic acids and CH1.
• Varied charge distributions on the protein to study their effect on coacervation.
• Analyzed coacervate formation, local ordering, and molecular diffusion at physiological ionic strengths.

Main Results:

• Coacervates readily formed at physiological ionic strengths, consistent with experimental observations.
• Increasing blockiness of protein charge distribution enhanced phase separation and local ordering.
• Extreme charge blockiness led to a segregated structure with significantly increased DNA ordering, similar to protamine-DNA complexes.

Conclusions:

• Complex coacervation is a robust mechanism for organizing nucleic acids and proteins in cellular environments.
• Protein sequence and charge distribution are critical determinants of coacervate properties and structure.
• Highly ordered condensed phases, driven by extreme charge blockiness, mirror natural systems like sperm chromatin condensation.