Elongation Factor Tu in Translation of mRNA

Elongation Factor Tu (EF-Tu) is a crucial component of the translation machinery that plays a central role in the elongation phase of protein synthesis in both prokaryotic and eukaryotic cells. EF-Tu functions as a GTPase enzyme and facilitates the accurate and efficient delivery of aminoacyl-tRNA (charged tRNA) molecules to the ribosome during translation.

Structure of EF-Tu

EF-Tu is a protein composed of approximately 400-450 amino acid residues, with a molecular weight of around 43-45 kDa in prokaryotes. It consists of three domains: the N-terminal domain (G domain), the central domain (domain II), and the C-terminal domain (domain III). The G domain contains the GTP-binding site and exhibits GTPase activity, while domains II and III are involved in tRNA binding and ribosome interaction.

Function of EF-Tu in Translation

The primary function of EF-Tu is to deliver aminoacyl-tRNA molecules to the ribosome during the elongation phase of translation.

This process involves several steps:

1. GTP Binding and Activation: EF-Tu initially binds to GTP in the cytoplasm, which induces a conformational change in the protein, leading to the exposure of the tRNA-binding site on domain II.
2. Aminoacyl-tRNA Binding: Once activated by GTP, EF-Tu forms a ternary complex with aminoacyl-tRNA (charged tRNA) molecules. Each aminoacyl-tRNA corresponds to a specific amino acid and carries the appropriate anticodon sequence that pairs with the mRNA codon during translation.
3. Delivery to the Ribosome: The ternary complex of EF-Tu-GTP and aminoacyl-tRNA is transported to the ribosome, where it binds to the A site (aminoacyl site) of the ribosome. The anticodon of the incoming tRNA base pairs with the complementary mRNA codon in the A site.
4. GTP Hydrolysis and tRNA Release: Upon correct codon-anticodon pairing and formation of the peptidyl transferase reaction, EF-Tu hydrolyzes GTP to GDP and inorganic phosphate (Pi). This hydrolysis reaction triggers a conformational change in EF-Tu, leading to the release of EF-Tu-GDP from the ribosome, along with the unbound GDP.

Accuracy and Fidelity of Translation

EF-Tu plays a critical role in ensuring the accuracy and fidelity of protein synthesis by discriminating between cognate (correctly paired) and near-cognate (incorrectly paired) aminoacyl-tRNA molecules. The binding of EF-Tu to cognate tRNA is favored energetically, resulting in a higher affinity and stability of the ternary complex compared to near-cognate tRNA. This discrimination process, known as tRNA selection, helps minimize errors in translation and ensures the faithful synthesis of proteins.

Regulation of EF-Tu Activity

The activity of EF-Tu is regulated by various factors, including GTP hydrolysis, ribosome binding, and interaction with other translation factors. GTP hydrolysis by EF-Tu is stimulated upon correct codon-anticodon pairing and peptide bond formation, leading to the release of EF-Tu-GDP from the ribosome. Additionally, regulatory proteins and small molecules can modulate the activity of EF-Tu, influencing the efficiency and fidelity of translation.

The Elongation Factor Tu (EF-Tu) plays a central role in the accurate and efficient delivery of aminoacyl-tRNA molecules to the ribosome during translation. By facilitating the selection and binding of cognate tRNA, EF-Tu helps ensure the fidelity of protein synthesis and contributes to the overall accuracy of the genetic code translation. Understanding the molecular mechanisms underlying EF-Tu function provides insights into fundamental processes of cellular biology and offers potential targets for therapeutic intervention in various diseases.