Role of pH in Modulating RNA-Protein Interactions in TRBP2-dsRBD2: An Interplay between Conformational Dynamics and...

Area of Science:

• Molecular Biology
• Biochemistry
• Structural Biology

Background:

• RNA-protein interactions are vital for cellular functions and disease mechanisms.
• Cellular stress, like hypoxia, lowers intracellular pH, affecting RNA-protein electrostatic interactions and protein structure.
• Understanding pH's role in modulating these interactions is critical for therapeutic development.

Purpose of the Study:

• To investigate the impact of pH on the interaction between TRBP2-dsRBD2 and dsRNA.
• To elucidate the combined effects of pH-induced conformational flexibility and electrostatic changes on RNA-binding.

Main Methods:

• Solution-state Nuclear Magnetic Resonance (NMR) spectroscopy was employed.
• NMR dynamics experiments were used to assess protein flexibility.
• Analysis of charge distribution on the protein surface was performed.

Main Results:

• A decrease in pH significantly increased the flexibility of TRBP2-dsRBD2, particularly at RNA-binding residues.
• Altered charge distribution on the protein surface was observed at lower pH.
• A dynamics-driven model was proposed, highlighting the counterbalance between electrostatic and conformational effects.

Conclusions:

• The binding affinity between TRBP2-dsRBD2 and dsRNA is governed by a delicate balance between conformational dynamics and electrostatic interactions.
• pH plays a crucial role in modulating RNA-protein interactions through both flexibility and electrostatics.
• These findings offer insights into the molecular mechanisms underlying pH-dependent biological processes.