Role of aaRS complexes in translation

Several studies have revealed the involvement of multi aminoacyl-tRNA synthetase complexes (MSC) in translation.  In eukaryotes these complexes tend to be larger than those discovered in bacteria and archaea and also perform a wider range of functions that include both aminoacylation and noncanonical roles beyond translation.

In archaeal methanogens, seryl-tRNA synthetase:arginyl-tRNA synthetase (SerRS:ArgRS) assembly is formed to enhance aminoacylation of serine-specific tRNAs especially under conditions of elevated temperature and salt concentration. Thus, such aaRSs complexes may constitute a part of thermo- and osmoadaptation mechanisms of thermophilic methanogenic archaea, by providing an optimal microenvironment that facilitates stable tRNA aminoacylation. Since each of the aaRSs are also involved in binary complexes with their cognate tRNAs, dynamic interplay between possible functional states are currentlly investigated. The SerRSs from methanogenic archaea differ markedly from their bacterial-type counterparts. An interesting question is whether observed regulation of enzyme activity via synthetase complex formation is an exclusive ability of methanogenic-type SerRSs. If so, this feature may influence evolutionary conservation of methanogenic-type SerRS forms in archaea that live in harsh environments. Similar rationale complies with projects in which we explore possibilities of improved aminoacylation error correction by associated aaRSs vs. unassociated enzymes and investigation whether new modes of aminoacylation proofreading parallel synthetase assembling.

Further, atypical methanogenic-type SerRS and an archaeal ArgRS bind to the large ribosomal subunit with micromolar affinities. We are interested in detailed study of SerRS:ArgRS complex binding to Methanothermobacter thermautotrophicus ribosomes. The interpretation of data is facilitated by cryo-EM reconstructed 3D structure of M. thermautotrophicus 50S ribosomal subunit. The interaction point with ribosome was narrowed down to several ribosomal proteins. All of them comprise the P0/P1 stalk and proteins near the P0/P1 stalk base of the 50S subunit. The interior of the cell is highly crowded with macromolecules, and tRNAs may not diffuse far after exiting the ribosome. Indeed, they may remain in the vicinity of the ribosome to be recharged and reused for another cycle of elongation.