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High-resolution imaging reveals ribosome dynamics in yeast cells

Ribosomal translation is the process by which cells synthesize proteins based on the genetic instructions encoded in messenger RNA. It is essential for life, yet it is an incredibly complex process involving multiple steps and the precise coordination of various molecules. It is challenging to capture the complete translation cycle using single-particle analysis (SPA) based on in vitro purification.

In a recent study in Nature Structural & Molecular Biology, researchers led by Prof. Zhang Xinzheng at the Institute of Biophysics, Chinese Academy of Sciences, utilized cryo-electron microscopy (cryo-EM) along with their self-developed algorithm, GisSPA, to capture dynamic, periodic changes in ribosomal translation within the cells of Saccharomyces cerevisiae—also known as Brewer's yeast—at near-atomic resolution.

This study provides detailed measurements of the movement parameters of the small subunit (SSU) during translation and illustrates the periodic binding of three elongation factors (eEF1A, eEF2, eEF3) to the ribosome as well as their dissociation from it.

For the first time, the researchers captured the compact form of eEF2 during peptidyl transfer, which contributes to stabilizing the environment for this process and optimizing its performance. Additionally, in the early stages of translocation, less extended conformations of eEF2 were observed. The entire lifecycle of eEF2 highlights its critical role as a "molecular arm" in both peptidyl transfer and translocation within eukaryotic cells.

Moreover, the study identified, for the first time, the fully rotated ribosome bound to the open form of eEF3. The researchers found that eEF3 binds to the ribosome early in translocation, with its conformational changes accompanied by the swiveling of the 40S head and the rotation of the 40S body.

This research thoroughly elucidates the dynamic multi-conformational characteristics of ribosomes during the translation process.

"Understanding the entire translation process in depth helps us better uncover the intricate mechanisms of protein synthesis and explore its critical roles in cellular functions, metabolic regulation, and disease development," said Prof. Zhang.