Intra-protein compensatory mutations analysis highlights the trna recognition regions in aminoacyl-trna synthetases

Milana Frenkel-Morgenstern, Dmitry Tworowski, Liron Klipcan, Mark Safro

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


The aminoacyl-tRNA synthetases (aaRSs) covalently attach amino acids to their corresponding nucleic acid adapter molecules, tRNAs. The interactions in the tRNA-aaRSs complexes are mostly non-specific, and largely electrostatic. Tracing a way of aaRS-tRNA mutual adaptation throughout evolution offers a clearer view of understanding how aaRS-tRNA systems preserve patterns of tRNA recognition and binding. In this study, we used the compensatory mutations analysis to explore adaptation of aaRSs in respond to random mutations that can occur in the tRNA-recognition area. We showed that the frequency of compensatory mutations among residues that belong to the recognition region is 1.75-fold higher than that of the exposed residues. The highest frequencies of compensatory mutations are observed for pairs of charged residues, wherein one residue is located within the tRNA-recognition area, while the second is placed outside of the area, and contributes to the formation of the aaRS electrostatic landscape. Given charged residues are compensated by buried charge residues in more than 60% of the analyzed mutations. The cytoplasmatic and mitochondrial aaRSs preserve similar patterns of compensatory mutations in the tRNA recognition areas. Moreover, we found that mitochondrial aaRSs demonstrate a significant increase in the frequency of compensatory mutations in the area. Our findings shed light on the physical nature of compensatory mutations in aaRSs, thereby keeping unchanged tRNA-recognition patterns.

Original languageEnglish
Pages (from-to)115-126
Number of pages12
JournalJournal of Biomolecular Structure and Dynamics
Issue number2
StatePublished - Oct 2009
Externally publishedYes

Bibliographical note

Funding Information:
The authors are grateful to A. Horovitz and M. Eisenstein for reading manuscript and valuable comments. This work is supported by the Center for Complexity Science, the Binational Science Foundation Grant no. 2005209 (to MS) and by the Kimmelman Center for Biomolecular Structure and Assembly. MS holds the Lee & William Abramowitz Professorial Chair of Molecular Biophysics.


  • Aminoacyl-tRNA synthetases
  • Compensatory mutation
  • Correlated mutation analysis
  • Trna
  • Trna-recognition region


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