Allosteric collaboration between elongation factor G and the ribosomal L1 stalk directs tRNA movements during translation

TL;DR

This study reveals how the L1 stalk's conformational changes, influenced by EF-G and tRNA, facilitate tRNA movement during translation, providing insights into the molecular mechanism of protein synthesis.

Contribution

It uncovers the allosteric collaboration between EF-G and the L1 stalk in directing tRNA translocation during translation.

Findings

L1 stalk exists in open and closed conformations during translation.

EF-G shifts L1 stalk towards the closed conformation via distinct kinetic mechanisms.

L1 stalk dynamics depend on the presence and identity of E-site tRNA.

Abstract

Determining the mechanism by which transfer RNAs (tRNAs) rapidly and precisely transit through the ribosomal A, P and E sites during translation remains a major goal in the study of protein synthesis. Here, we report the real-time dynamics of the L1 stalk, a structural element of the large ribosomal subunit that is implicated in directing tRNA movements during translation. Within pre-translocation ribosomal complexes, the L1 stalk exists in a dynamic equilibrium between open and closed conformations. Binding of elongation factor G (EF-G) shifts this equilibrium towards the closed conformation through one of at least two distinct kinetic mechanisms, where the identity of the P-site tRNA dictates the kinetic route that is taken. Within post-translocation complexes, L1 stalk dynamics are dependent on the presence and identity of the E-site tRNA. Collectively, our data demonstrate that EF-G and the L1 stalk allosterically collaborate to direct tRNA translocation from the P to the E sites, and suggest a model for the release of E-site tRNA.