Phosphorylation decelerates conformational dynamics in bacterial translation elongation factors

Area of Science:

• Bacteriology
• Molecular Biology
• Biochemistry

Background:

• Bacterial protein synthesis is linked to metabolic rate.
• Bacteria modify translation factors post-translationally to adapt to environmental stress.
• Phosphorylation of EF-Tu is critical for stationary phase entry and sporulation.

Purpose of the Study:

• To investigate the mechanism by which phosphorylation inactivates Escherichia coli EF-Tu.
• To elucidate the role of EF-Tu phosphorylation in bacterial stress response and metabolism.

Main Methods:

• Structural analysis of EF-Tu.
• Biophysical characterization of EF-Tu phosphorylation.
• Investigating the effects of modifications on EF-Tu dynamics and nucleotide binding.

Main Results:

• Phosphorylation of EF-Tu at T382 acts as a switch, decoupling nucleotide binding from the conformational cycle.
• Modifications stabilizing the switch I region create a conformational trap, restricting EF-Tu dynamics.
• This mechanism explains phosphoregulation of bacterial translation and metabolism.

Conclusions:

• Phosphorylation-induced conformational traps are key to regulating bacterial translation and metabolism.
• This mechanism likely underlies multisite phosphorylation observed during bacterial dormancy and stationary phase.