EF-Tu and EF-G are activated by allosteric effects.

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• GTPases are crucial regulators of cellular processes.
• Quantitative understanding of GTPase activation, particularly free-energy surfaces, remains a challenge.
• Elucidating the catalytic mechanisms of GTPase reactions is essential.

Purpose of the Study:

• To investigate the energetics of EF-G and EF-Tu activation by the ribosome.
• To explore the catalytic mechanisms of the GTPase reaction.
• To validate computational findings using mutational data.

Main Methods:

• Computational analysis of free-energy surfaces for EF-G and EF-Tu.
• Comparison of EF-Tu and EF-G structures and energetics.
• Inclusion of mutational effects for validation.

Main Results:

• The GTPase reaction can proceed via a two-water or a one-water (GTP as a base) mechanism.
• Both mechanisms involve a structural allosteric effect during activation.
• Comparison revealed potential issues with existing EF-Tu structural data.

Conclusions:

• A structural allosteric effect is a likely general activation mechanism for all GTPases.
• The findings provide quantitative insights into GTPase reaction energetics.
• This study offers a validated framework for understanding GTPase function.