EFTuGTPaminoacyltRNA

EFTuGTPaminoacyltRNA refers to the ternary complex formed by elongation factor Tu (EF-Tu) bound to GTP and an aminoacyl-tRNA (aa-tRNA). In bacteria, this complex delivers aminoacyl-tRNA to the ribosome during protein synthesis and is essential for accurate elongation.

Formation and composition: Aminoacyl-tRNA is produced by aminoacyl-tRNA synthetases, which charge tRNAs with their cognate amino acids. EF-Tu binds GTP and the aa-tRNA to form EF-Tu-GTP-aa-tRNA. EF-Ts acts as a guanine nucleotide exchange factor, recycling EF-Tu•GDP back to EF-Tu•GTP in the cytosol.

Mechanism of action and fidelity: The ternary complex associates with the ribosomal A site. If the codon-anticodon pairing is correct, conformational changes promote GTP hydrolysis by EF-Tu, leading to the release of EF-Tu•GDP and the accommodation of the aa-tRNA into the peptidyl transferase center for peptide bond formation. If the pairing is incorrect, GTP hydrolysis is slowed and the complex dissociates, reducing misincorporation.

Structure and regulation: EF-Tu comprises three domains, with domain I housing the GTPase activity, and domains II and III supporting tRNA binding. GTP binding and hydrolysis induce conformational shifts that modulate affinity for aa-tRNA and the ribosome. The entire system is regulated by nucleotide availability and by EF-Ts, which regenerates the active EF-Tu•GTP pool.

Clinical and research notes: The EF-Tu–GTP–aa-tRNA complex is a target for antibiotics that disrupt translation, such as kirromycin, which blocks release of the aa-tRNA from EF-Tu. In eukaryotes, a functional homolog exists as eEF1A with a similar role.