Translational GTPases (trGTPases) play key roles in facilitating protein synthesis on the ribosome. Despite the high degree of evolutionary conservation in the sequences of their GTP-binding domains, the rates of GTP hydrolysis and nucleotide exchange vary broadly between different trGTPases. EF-Tu, one of the best-characterized model G proteins, evolved an exceptionally rapid and tightly regulated GTPase activity, which ensures rapid and accurate incorporation of amino acids into the nascent chain. Other trGTPases instead use the energy of GTP hydrolysis to promote movement or to ensure the forward commitment of translation reactions. Recent data suggest the GTPase mechanism of EF-Tu and provide an insight in the catalysis of GTP hydrolysis by its unusual activator, the ribosome. Here we summarize these advances in understanding the functional cycle and the regulation of trGTPases, stimulated by the elucidation of their structures on the ribosome and the progress in dissecting the reaction mechanism of GTPases. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 463–475, 2016.

The elongation phase of translation is promoted by three universal elongation factors, EF-Tu, EF-Ts, and EF-G in bacteria and their homologs in archaea and eukaryotes. Recent findings demonstrate that the translation of a subset of mRNAs requires a fourth elongation factor, EF-P in bacteria or the homologs factors a/eIF5A in other kingdoms of life. EF-P prevents the ribosome from stalling during the synthesis of proteins containing consecutive Pro residues, such as PPG, PPP, or longer Pro clusters. The efficient and coordinated synthesis of such proteins is required for bacterial growth, motility, virulence, and stress response. EF-P carries a unique post-translational modification, which contributes to its catalytic proficiency. The modification enzymes, which are lacking in higher eukaryotes, provide attractive new targets for the development of new, highly specific antimicrobials. © 2013 Wiley Periodicals, Inc. Biopolymers 99: 837–845, 2013.