Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• Ribosomal frameshifting expands the coding repertoire of cells and viruses.
• The precise mechanism and timing of +1 frameshifting during translation elongation are not fully understood.

Purpose of the Study:

• To elucidate the structural basis of +1 ribosomal frameshifting during translation elongation.
• To visualize the role of elongation factor G (EF-G) in the frameshifting process.

Main Methods:

• Cryo-electron microscopy (cryo-EM) at ~3.5-Å resolution.
• Structural analysis of 70S ribosome complexes during elongation and translocation.
• Investigation of ribosome complexes with +1-frameshifting-prone mRNA and EF-G.

Main Results:

• Seven cryo-EM structures revealed the dynamics of ribosome elongation and EF-G mediated translocation.
• +1 frameshifting was observed to occur during the translocation of tRNA and mRNA.
• EF-G•GDPCP binding induces tRNA shift to the +1 frame, causing mRNA bulging and ribosome frameshifting.

Conclusions:

• The ribosome and EF-G work together to induce +1 frameshifting.
• Frameshifting occurs during the translocation step of translation.
• This mechanism contributes to the expansion of cellular and viral coding potential.