Aminoacyl-tRNA synthetases (aaRSs) are multi-domain proteins that catalyze covalent attachment of amino acids to the 3'-end of the cognate tRNA molecules. Long-range domain-domain communications are known to play an important role in the function of aaRSs. Earlier studies have demonstrated that the coupling of domain motions is important in mediating long-range inter-domain communication in modular proteins (1). However, the molecular mechanism of coupled-domain motions and long-range communication in aaRSs has remained poorly understood. In the present study, the molecular mechanism underlying the coupled-domain motions in aaRSs has been probed. Specifically, a bioinformatics-based analysis has been performed to trace �pre-existing� interaction networks that facilitate coupled-domain dynamics. Herein, we will report the Statistical Thermal Coupling Analysis (STCA) method, which integrates the information of dynamic coupling of residues with their evolutionary features (conservation and coevolution). The STCA method is applied to three aaRS systems: methionyl-, leucyl- and glutaminyl,-prolyl-tRNA synthetases. The present study demonstrates that the dynamic coupling among distant domains of these aaRSs is maintained through networks of evolutionarily constrained residues that are engaged in correlated motion. Moreover, multiple residue-residue interaction networks between distant functional domains are revealed in this study. Existence of these interaction networks is consistent with mutational data and is supported by computational studies.  References: 1) Weimer,  K. M., Shane,  B. L., Brunetto, M., Bhattacharyya S., Hati S. (2009) J. Biol. Chem. 284, 10088-10099.

Application of statistical-thermal coupling analysis to identify residue-residue interaction networks that facilitate coupled-domain dynamics in aminoacyl-tRNA synthetases

243rd National Meeting (2012)

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