Structural characterization of human aminoacyl-tRNA synthetases for translational and nontranslational functions

- Human tRNA synthetases mediate diverse functions.
- Structural analyses help to understand the novel functions.
- Crystallography analysis determines static structures of human tRNA synthetases.
- Small angle X-ray scattering (SAXS) determines structural dynamics of human tRNA synthetases.
- Hydrogen/deuterium exchange (HDX) determines complex interface and structural regulation of human tRNA synthetases.

Aminoacyl-tRNA synthetases (aaRSs) are enzymes that function at the first step of translation, catalyzing the conjugation of amino acids to their cognate tRNAs for protein synthesis. While preserving this essential role, higher eukaryotic aaRSs, such as human cytoplasmic aaRSs, have developed other functions during evolution, including angiogenesis, inflammation, development, tumorigenesis, etc. These translational and nontranslational functions of aaRSs are attractive targets for developing antibacterial, antifungal, anticancer agents and for treating other human diseases. Structural characterization of aaRS functions in both categories has deepened our understanding and provided insightful platform for further structure-based drug design. The convergence of the mechanism of action, together with their divergent functions, offers a possible protocol for studying these features of aaRSs in general. To guide this objective in future, we provide here a review on the methods used in structural analysis, which may be applied to study this special group of housekeeping proteins.