engleski

Accuracy of translation : Lessons from aminoacyl-tRNA synthetases

Aminoacly-tRNA synthetases catalyze the specific linkage of an amino acid to its cognate tRNA isoacceptors. The accuracy of this reaction is essential to the fidelity of protein synthesis and hence cell survival. Aminoacylation proceeds in two steps. First, the amino acid is activated by reaction with ATP to yield an aminoacyl adenylate intermediate and pyrophosphate. In the second step, amino acid is transfered to tRNA producing aminoacly-tRNA with release of AMP. To obtain a high level of specificity in tRNA recognition, synthetases utilize an extensive network of interactions that participate in direct and indirect readout of cognate macromolecular substrate. The way of recognition of tRNA by cognate synthetase could vary between domains of life. Differences between modes of seryl-tRNA synthetase:tRNA interaction and communication in yeast and methanogenic archaea will be discussed. Accurate recognition of cognate amino acid is more challenging because of similar sizes and/or chemical structures of many amino acid side chains. As a result, misactivation of non-cognate amino acid and misacylation of cognate tRNA can occur. To correct these errors, some synthetases have evolved energetically expensive hydrolytic editing or proofreading mechanism. It is well established that correction of misacylated tRNA (post-transfer editing) occurs in a second, spatially separated, active site located on an “ editing domain” . However, the exact place and mechanism of pre-transfer editing (hydrolysis of misactivated amino acid) is still an open question. Our data suggest that non-cognate aminoacyl-adenylate could be corrected in the hydrolytic site that is spatially adjacent or overlapping with the synthetic active site rather than in the separate domain used for post-transfer editing. In many systems, tRNA plays important role in amino acid recognition by influencing synthetase’ s specificity and catalytic efficiency in aminoacyl adenylate formation. Glutaminyl-tRNA synthetase does not activate glutamine in the absence of tRNA specific for glutamine (tRNAGln). Interaction with tRNA repositions key active site peptides that bind glutamine and ATP. In addition to its structural role, we have recently demonstrated a direct catalytic involvement of tRNAGln in glutaminyl adenylate formation.

hydrolytic editing; aminoacyl-tRNA synthetases; pre-transfer editing

nije evidentirano