Molecular insights into the interaction between a disordered protein and a folded RNA

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Intrinsically disordered protein regions (IDRs) are crucial for protein interactions and biomolecular condensate formation.
• RNA-binding proteins (RBPs) utilize IDRs alongside structured domains for their functions.

Purpose of the Study:

• To characterize the RNA-binding properties of Small ERDK-Rich Factor (SERF), a small, positively charged IDR-containing protein.
• To investigate the structural and dynamic changes in SERF upon binding to RNA using biophysical methods and simulations.

Main Methods:

• Solution-state biophysical techniques (e.g., NMR, SAXS) were employed.
• Molecular dynamics simulations were performed.
• Characterization of SERF alone and in complex with HIV-1 Trans-Activation Response (TAR) RNA fragment.

Main Results:

• SERF and RNA undergo charge-driven phase separation at high concentrations.
• SERF binding to RNA does not induce significant structural changes in either molecule.
• A modest global compaction of the SERF ensemble was observed upon RNA binding, suggesting attenuated charge repulsion.

Conclusions:

• The SERF-RNA interaction provides a model system for studying IDR-RNA dynamics.
• Attenuated charge repulsion in SERF upon RNA binding contributes to higher-order assembly.
• Understanding IDR-RNA contacts is key to comprehending complex formation and liquid-liquid phase separation.