Mechanism of the difference in the binding affinity of E. coli tRNAGln to glutaminyl-tRNA synthetase caused by noninterface nucleotides in variable loop.

Aminoacyl-tRNA synthetases (ARSs) distinguish their cognate tRNAs from many other kinds of tRNAs, despite the very similar tertiary structures of tRNAs. Many researchers have supported the view that this recognition is achieved by intermolecular interactions between tRNA and ARS. However, one of the aptamers of Escherichia coli glutamine specific tRNA, var-AGGU, has a higher affinity to ARS than the wild-type, although the sequence difference only lies in the variable loop located on the opposite side of the binding interface with ARS. To understand the reason for the difference in affinity, we did molecular dynamics simulations on tRNAs and their complexes with ARS. We calculated the enthalpic and entropic contributions to the binding free energy with the molecular mechanics-Poisson-Boltzmann/surface area method and found that the entropic difference plays an important role in the difference in binding free energies. During the molecular dynamics simulations, dynamic rearrangements of hydrogen bonds occurred in the tertiary core region of the wild-type tRNA, whereas they were not observed in the free var-AGGU simulation. Since the internal mobility was suppressed upon complex formation with ARS, the entropy loss in the wild-type was larger than that of the aptamer. We therefore concluded that the sequence difference in the variable loop caused the difference in the internal mobility of the tertiary core region tRNAs and led to the difference in the affinity to ARS through the entropy term.

Citation

Satoshi Yamasaki, Shugo Nakamura, Tohru Terada, Kentaro Shimizu. Mechanism of the difference in the binding affinity of E. coli tRNAGln to glutaminyl-tRNA synthetase caused by noninterface nucleotides in variable loop. Biophysical journal. 2007 Jan 1;92(1):192-200

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PMID: 17028132

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