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https://doi.org/10.5562/cca4270

Catalytic and Accessory Domains Jointly Ensure the Functional Fold of Isoleucyl-tRNA Synthetase

Igor Zivkovic ; University of Zagreb Faculty of Science, Department of Chemistry, Horvatovac 102a, 10000 Zagreb, Croatia
Melody Skulac ; University of Zagreb Faculty of Science, Department of Chemistry, Horvatovac 102a, 10000 Zagreb, Croatia
Ita Gruic-Sovulj ; University of Zagreb Faculty of Science, Department of Chemistry, Horvatovac 102a, 10000 Zagreb, Croatia *

* Dopisni autor.

Sažetak

Aminoacyl-tRNA synthetases (AARSs) covalently couple amino acids to their cognate tRNAs, providing aminoacyl-tRNAs for ribosomal protein synthesis. Given their essential role and the challenge of maintaining high fidelity despite the presence of similar amino acids and tRNAs in the cell, AARSs have acquired various domains, making them interesting models for studying protein modularity. Here, we used Priestia megaterium isoleucyl-tRNA synthetase (IleRS) to explore how the simultaneous removal of multiple domains distant from the aminoacylation active site affects activity. Yet we found that eliminating editing and C-terminal domains, with or without further removal of the CP2 domain, drastically increases IleRS propensity for aggregation. We succeeded in producing a small amount of the soluble truncated variant, which showed about a 4,000-fold decrease in activity. Our data suggest that during the evolution of IleRS, accessory domains couple with the rest of the protein scaffold to maintain the productive fold of the active site.

Ključne riječi

AARS – aminoacyl-tRNA synthetase; AA-AMP – aminoacyl-adenylate; AMP – adenosine 5’-monophosphate; ATP – adenosine 5’-triphosphate; CP1 – connective peptide 1; CP2 – connective peptide 2; IleRS – isoleucyl-tRNA synthetase; LeuRS – leucyl-tRNA synthetase; PPi – pyrophosphate; SerRS – seryl-tRNA synthetase

Hrčak ID:

348348

URI

https://hrcak.srce.hr/348348

Datum izdavanja:

21.5.2026.

Posjeta: 0 *