Elongation factor Tu–aminoacyl-tRNA complex (EF-Tu:aa-tRNA complex)

The elongation factor Tu–aminoacyl-tRNA complex is a central protein–nucleic acid assembly in bacterial translation elongation. EF-Tu is a highly conserved bacterial GTPase that binds aminoacyl-tRNA (aa-tRNA) in its GTP-bound form, forming a ternary complex (EF-Tu–GTP–aa-tRNA) that delivers the correct aa-tRNA to the ribosomal A-site according to the mRNA codon sequence. Upon correct codon–anticodon pairing, EF-Tu hydrolyzes GTP, undergoes a conformational change, and releases the tRNA into the ribosome for peptide bond formation, before being recycled in a GTP-dependent manner with the help of EF-Ts. EF-Tu is an essential and ancient translation factor, and its complex with aa-tRNA is a validated antibacterial drug target, with several natural product antibiotics inhibiting this pathway by locking EF-Tu to the tRNA and impairing protein synthesis. Because of its essential role in bacterial viability and highly conserved structure, but significant divergence from eukaryotic homologs, EF-Tu is considered to be an attractive, though not entirely risk-free, therapeutic target for new antibacterial agents.

Other names

Elongation factor Tu–tRNA complexEF-Tu ternary complexEF-Tu–GTP–aminoacyl-tRNA complex

Inhibition of EF-Tu GTPase activity; Stabilization of EF-Tu:tRNA complex, preventing release of aminoacyl-tRNA; Blocking binding of EF-Tu to the ribosome; Preventing recycling of EF-Tu (by inhibiting EF-Ts-mediated GDP-GTP exchange)