Transient ion-mediated interactions regulate subunit rotation in a eukaryotic ribosome.

Area of Science:

• Computational Biology
• Biophysics
• Molecular Biophysics

Background:

• Ions are crucial for RNA folding, but their role in dynamic conformational changes remains unclear.
• Understanding ion-mediated interactions is key to deciphering RNA's functional mechanisms.

Purpose of the Study:

• To develop a theoretical model for simulating ion-RNA interactions at all-atom resolution.
• To investigate the influence of ions on RNA conformational rearrangements and biological processes.

Main Methods:

• Developed a theoretical model incorporating explicit electrostatics and ions (K+, Cl-, Mg2+).
• Validated the model using established RNA systems (58-mer and Ade riboswitch).
• Applied the model to simulate the yeast ribosome and analyze ion-dependent energy landscapes.

Main Results:

• The model accurately captures concentration-dependent ionic environments and ion types (chelated, hydrated).
• Simulations revealed that millimolar changes in magnesium chloride ([MgCl2]) affect ribosome intersubunit rotation energetics.
• Ion concentration shifts alter the distribution of rotational states and kinetics by over an order of magnitude.

Conclusions:

• Transient ion-mediated interactions, including inner-shell and outer-shell, directly regulate ribosomal subunit rotation.
• This provides a physical basis for how ions modulate large-scale biological processes like protein synthesis.
• The findings highlight the critical role of the ionic environment in RNA dynamics and function.