Molecular dynamics of EF-G during translocation

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• Elongation factor G (EF-G) is essential for mRNA-tRNA translocation during protein synthesis.
• EF-G undergoes dynamic conformational changes, visualized by cryo-EM and X-ray, but the precise molecular mechanisms remain unclear.

Purpose of the Study:

• To elucidate the molecular motions and conformational dynamics of EF-G during translocation using molecular dynamics simulations.
• To understand how EF-G's structural changes facilitate the movement of tRNAs and mRNA relative to the ribosome.

Main Methods:

• Molecular dynamics (MD) simulations of EF-G in solution.
• Analysis of domain rotations, loop flexibility, and interactions within EF-G.

Main Results:

• Identified rotations between EF-G's super-domains (I-II and III-V) and within Domain IV.
• Revealed flexible conformations of the 503- and 575-loops and significant conformational variability upon GTPase-associated center interaction.
• Highlighted the role of the Switch I region in mediating Domain IV conformational changes post-GTP hydrolysis, crucial for codon-anticodon helix disengagement.

Conclusions:

• MD simulations provide insights into the dynamic conformational landscape of EF-G during translocation.
• Specific domain movements and loop flexibilities are critical for EF-G's function in ribosome translocation.
• GTP hydrolysis and subsequent conformational changes, particularly involving Switch I and Domain IV, are key to releasing tRNA from the decoding center.