Elongating without arms

Abstract

The GTPase elongation factor Tu (EF-Tu, also called EF-1a) is a workhorse of the cellular translation machinery. Its task is to provide substrates for protein synthesis by collecting and delivering aminoacyl tRNAs to the A-site of the ribosome. An inherent property of EF-Tu is its ability to recognize all manner of aminoacyl tRNAs in preference to uncharged tRNA. This broad specificity is achieved by simultaneous recognition of the aminoacylated acceptor stem A-form helix and the T-arm of tRNA, as shown by both structural and functional studies. The finding that selenocysteinyl tRNAs, which contain an additional base pair, instead bind the alternative elongation factor SelB emphasized the importance of the acceptor stem in EF-Tu binding. Now, Ohtsuki et al. [1xA unique serine-specific elongation factor Tu found in nematode mitochondria. Ohtsuki, T. et al. Nat. Struct. Biol. 2002; 9: 669–673Crossref | PubMed | Scopus (31)See all References[1] have discovered elongation factors that bind particular aminoacyl tRNAs lacking either D- or T-arms, shedding new light on the specificity of recognition by EF-Tu.The first suggestions that elongation factors of divergent specificity might exist came from extensive studies of eukaryotic mitochondrial tRNAs, several of which are highly unusual in that they lack canonical structures. For example, it has been found that in nematode mitochondria, most tRNAs lack T-arms whilst serine tRNAs contain T-arms but lack D-arms. This led Ohtsuki et al. to search for mitochondrial EF-Tu homologues in Caenorhabditis elegans. Their original studies had already identified one protein (EF-Tu1) that specifically recognized tRNAs lacking a T-arm, but not tRNAsSer. This most recent study has now revealed a second mitochondrially targeted EF-Tu homologue (EF-Tu2) that, as expected, only binds tRNAsSer lacking D-arms. During these studies, Ohtsuki et al. also noted that the amino-acid binding-site sequence of EF-Tu2 is highly divergent, leading them to study the specificity of the protein for the aminoacyl moiety. From examining different aminoacyl moieties, it was shown that not only is EF-Tu2 specific for tRNAsSer lacking D-arms, it is also able to discriminate against amino acids other than serine when they are attached to these tRNAs. This recognition of both the aminoacyl and tRNA moieties reveals a level of substrate discrimination consistent with recent suggestions that elongation factors provide important points of quality control during protein synthesis.One of the most remarkable aspects of EF-Tu1 and EF-Tu2 is that their novel functionality is apparently realized by the addition of short peptide motifs at their C-termini. The elucidation of how these relatively small structural changes can lead to such profound functional modifications will provide enormous insight into the workings of elongation factors. The discovery of two forms of EF-Tu, each responsible for structurally discrete elongator aminoacyl tRNA populations, also deepens the mystery as to why these unusual tRNAs are so prevalent in some systems, and questions how they and their EF-Tu partners arose.