Ribosome Elongation Kinetics of Consecutively Charged Residues Are Coupled to Electrostatic Force

Area of Science:

• Molecular Biology
• Biophysics
• Computational Biology

Background:

• Ribosome protein synthesis speed is modulated by the sequence of amino acids.
• The molecular mechanisms underlying this sequence-dependent speed regulation are not fully understood.

Purpose of the Study:

• To elucidate the molecular origins of how charged residues affect protein synthesis speed.
• To investigate the role of mechanochemistry in mediating translation speed changes.

Main Methods:

• Multiscale simulations were employed to model the interactions of charged residues within the ribosome.
• Analysis focused on forces exerted by charged residues on adjacent amino acids and their impact on transition state barriers.

Main Results:

• Positively charged residues push P-site amino acids away from A-site amino acids, increasing the peptide bond formation barrier.
• Negatively charged residues pull A- and P-site amino acids closer, decreasing the peptide bond formation barrier.
• These forces mechanochemically alter translation speed.

Conclusions:

• A mechanochemical mechanism explains how charged residues influence translation speed.
• This mechanism is consistent with in vivo ribosome profiling and experimental data.
• The findings provide a framework for understanding sequence-based translation dynamics.