Transfer RNA recognition by aminoacyl-tRNA synthetases

Abstract

The aminoacyl‐tRNA synthetases are an ancient group of enzymes that catalyze the covalent attachment of an amino acid to its cognate transfer RNA. The question of specificity, that is, how each synthetase selects the correct individual or isoacceptor set of tRNAs for each amino acid, has been referred to as the second genetic code. A wealth of structural, biochemical, and genetic data on this subject has accumulated over the past 40 years. Although there are now crystal structures of sixteen of the twenty synthetases from various species, there are only a few high resolution structures of synthetases complexed with cognate tRNAs. Here we review briefly the structural information available for synthetases, and focus on the structural features of tRNA that may be used for recognition. Finally, we explore in detail the insights into specific recognition gained from classical and atomic group mutagenesis experiments performed with tRNAs, tRNA fragments, and small RNAs mimicking portions of tRNAs. © 2000 John Wiley & Sons, Inc. Biopoly 52: 1–28, 1999

Towards deciphering the principles underlying an mRNA recognition code

“…The other recognition determinant, the conserved bulged C8, is sandwiched between two arginines within a small pocket and is involved in base-specific hydrogen bonds with the side chain of S681 and backbone of P682, D781, and W782 (lower left panel in Figure 3c). The availability of two separated RNA-binding sites, which recognize the loop and bulged cytosine, greatly increase the selectivity of IRE recognition by IRP-1, thereby resembling the two-point recognition reported previously in tRNA-aminoacyl-tRNA synthetase and some RNA-ribosomal protein complexes [32,33].…”

Self-Referential Encoding on Modules of Anticodon Pairs—Roots of the Biological Flow System

“…Evolution of synthetase/anticodon interactions. The data, compiled from [32] are consistent with the proposition that the initial encoding of a (proto)tRNA is dictated by the protein (synthetase) binding to it, which may or may not involve the anticodon. When it involves the anticodon, it is directed to the principal dinucleotide, which means a full box degeneracy, the 5' base being N. Evolution of proteins with the enlarged amino acid 'alphabet', required creation of some multi-meaning boxes, which is accompanied by interaction of the synthetase with all three positions in the anticodon.…”

“…Since the prebiotic oligomers proposed to have started the dimer-directed protein synthesis (DDPS) are not known, a proxy would be the readily available small RNAs than can self-aminoacylate [132,133] or the kinds of minitRNAs or mini-helices that have been utilized as substitutes for the acceptor arm of tRNAs [32]. In both cases, the oligomer sets should contain segments or loops that would provide the dimerization ability and tails that would carry the amino acid.…”

Unraveling the essential role of CysK in CDI toxin activation

“…We hypothesize that Trp176 stacks onto nucleobases within the tRNA anticodon loop. This mode of recognition is common among aminoacyl-tRNA synthetases, which bind cognate tRNAs using conserved hydrophobic/aromatic residues that stack onto the first and second nucleotides of the anticodon (28).…”