Michael Ibba

ibba.1@osu.edu 

lab page

Associate Professor

Ph.D. University of Manchester '90
Post-doc. Ciba, ETH-Zurich, Yale University '90-'98

Assc. Res. Prof. Copenhagen University '99-'01

Protein synthesis in bacteria and archaea.
Antibiotic resistance.

Microbial protein synthesis
Ribosomes are the protein synthesis factories of the cell that translate the codons of mRNA into amino acids. Protein synthesis proceeds by delivery to the ribosome of aminoacyl-tRNAs, which pair with the corresponding mRNA sequences. Aminoacyl-tRNAs are made by the aminoacyl-tRNA synthetases, a family of twenty proteins each of which pairs a particular amino acid with the correct tRNA. Our work is directed towards trying to understand the underlying principles that determine substrate specificity during aminoacyl-tRNA synthesis.

The role of aminoacyl-tRNA in protein synthesis.

Click on image for movie (from National Human Genome Research Institute).

Antibiotic resistance
The aminoacyl-tRNA synthetases can be divided into two structurally unrelated classes (I and II) of ten members each, where a synthetase with particular substrate specificity will always belong to the same class regardless of its biological origin. We discovered that the lysyl-tRNA synthetases are class I enzymes (LysRS1) in certain archaea and bacteria but are otherwise members of class II (LysRS2). LysRS1 and LysRS2 contribute to the virulence of many bacterial pathogens by modulating antibiotic resistance through mechanisms which to date have only been minimally defined. We are working to define the roles of class 1 and class 2 lysyl-tRNA synthetases in establishing antibiotic resistance, and to determine if the corresponding pathways can be used as targets for anti-infective agents.

Model for RNA-dependent editing by phenylalanyl-tRNA

synthetase (Roy et al. 2004, EMBO Journal)

Quality control in aminoacyl-tRNA synthesis
Accurate aminoacyl-tRNA synthesis often requires an additional editing activity intrinsic to many aaRSs. The editing activity significantly decreases the level of mistakes in aminoacyl-tRNA synthesis in vitro and in vivo, although quantitative analysis of its contribution to the overall fidelity of translation has not been performed. The overall aim of our work is to develop experimental systems to quantitatively measure the frequency of aaRS-dependent misincorporation for several amino acids and evaluate the contribution of aaRS editing to overall translational fidelity.

Ling, J., Reynolds, N. and Ibba, M. 2009. Aminoacyl-tRNA synthesis and translational quality control. Annual Reviews of Microbiology. In Press. (PDF)

Ataide, S.F., Rogers, T.E. and Ibba, M. 2009. The CCA anticodon specifies separate functions inside and outside translation in Bacillus cereus. RNA Biology. In Press.

Ling, J., So, B.R., Yadavalli, S.S., Roy, H., Shoji, S., Fredrick, K., Musier-Forsyth, K. and Ibba, M. 2009. Resampling and editing of mischarged tRNA prior to translation elongation. Molecular Cell 33, 654-660. (PDF)

Fredrick, K. and Ibba, M. 2009. Errors rectified in retrospect. Nature 457, 157-158. (PDF).

Roy, H., Dare, K. and Ibba, M. 2009. Adaptation of the bacterial membrane to changing environments using aminoacylated phospholipids. Molecular Microbiology 71, 547-550. (PDF).

Yadavalli, S.S., Musier-Forsyth, K. and Ibba, M. 2008. The return of pre-transfer editing in protein synthesis. Proceedings of the National Academy of Sciences USA. 105, 19031-19032 (PDF).

Hausmann, C.D. and Ibba, M. 2008. Structural and functional mapping of the archaeal multi-aminoacyl-tRNA synthetase complex. FEBS Letters 582, 2178-2182 (PDF).

Hausmann, C.D. and Ibba, M. 2008. Aminoacyl-tRNA synthetase complexes: molecular multitasking revealed. FEMS Microbiology Reviews 32, 705-721 (PDF).

Roy, H. and Ibba, M. 2008. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proceedings of the National Academy of Sciences USA. 105, 4667-4672. (PDF). Comments in: PNAS, ACS Chem Biol

Roy, H. and Ibba, M. 2008. Monitoring Lys-tRNA^Lys phosphatidylglycerol transferase activity. Methods 44, 164-169.(PDF)

Ibba, M. 2008. Methods for studying aminoacyl-tRNA. Methods 44, 73. (Special Issue)

Ataide, S.F., Wilson, S.N., Dang, S., Rogers, T.E., Roy, B., Banerjee, R., Henkin, T.M. and Ibba, M. 2007. Mechanisms of resistance to an amino acid antibiotic that targets translation. ACS Chemical Biology 2, 819-827.(PDF)

Hausmann, C.D., Prætorius-Ibba, M. and Ibba, M. 2007. An aminoacyl-tRNA synthetase:elongation factor complex for substrate channeling in archaeal translation. Nucleic Acids Research 35, 6094-6102. (PDF).

Ling, J., Yadavalli, S. and Ibba, M.  2007. Phenylalanyl-tRNA synthetase editing defects result in efficient mistranslation of phenylalanine codons as tyrosine. RNA 13, 1881-1886. (PDF).

Ling, J., Roy, H., Qin, D., Rubio, M.A., Alfonzo, J.D., Fredrick, K. and Ibba, M. 2007. Pathogenic mechanism of a human mitochondrial tRNA^Phe mutation associated with MERRF syndrome. Proceedings of the National Academy of Sciences USA 104, 15299-15304. (PDF).

Levengood, J., Roy, H., Ishitani, R., Söll, D., Nureki, O., and Ibba, M. 2007. Anticodon recognition and discrimination by the a-helix cage domain of class I lysyl-tRNA synthetase. Biochemistry 46, 11033-11038. (PDF)

Ling, J., Roy, H. and Ibba, M.  2007. Mechanism of tRNA-dependent editing in translational quality control. Proceedings of the National Academy of Sciences USA. 104, 72-77. (PDF)

Prætorius-Ibba, M., Hausmann, C., Paras, M., Rogers, T.E. and Ibba, M.  2007. Functional association between three archaeal aminoacyl-tRNA synthetases. Journal of Biological Chemistry 282, 3680-3687. (PDF)

Hausmann, C.D., Ling, J. and Ibba, M.  2007. The unnatural culture of amino acids. Nature Methods 4, 205-206. (PDF)

Godinic, V., Mocibob, M., Rocak, S., Ibba, M.  and Weygand-Durasevic, I. 2007. Peroxin Pex21p interacts with C-terminal noncatalytic domain of yeast seryl-tRNA synthetase and forms a specific ternary complex with tRNA^Ser. FEBS Journal 274, 2788-2799. (PDF)

Rubio, M.A.T., Ragone, F.L., Gaston, K.W., Ibba, M. and Alfonzo, J.D. 2006. C to U editing stimulates A to I editing in the anticodon loop of a cytoplasmic threonyl tRNA in Trypanosoma brucei. Journal of Biological Chemistry 281, 115-120. (PDF)

Wang, S., Prætorius-Ibba, M., Ataide, S., Roy, H. and Ibba, M. 2006. Discrimination of cognate and non-cognate substrates at the active site of class I lysyl-tRNA synthetase. Biochemistry 45, 3646-3652. (PDF)

Ataide, S.A. and Ibba, M. 2006. Small molecules - big players in the evolution of protein synthesis. ACS Chemical Biology 1, 285 - 297. (PDF)

Metlitskaya, A., Kazakov, T., Kommer, A., Pavlova, O., Prætorius-Ibba, M., Ibba, M. Krasheninnikov, I., Kolb, V., Khmel, I. and Severinov, K. 2006. Aspartyl-tRNA synthetase is the target of peptidenucleotide antibiotic Microcin C. Journal of Biological Chemistry 281, 18033 - 18042. (PDF)

Roy, H. and Ibba, M. 2006. Phenylalanyl-tRNA synthetase contains a dispensable RNA binding domain that contributes to editing of non-cognate aminoacyl-tRNA. Biochemistry 45, 9156 - 9162. (PDF)

Roy, H. and Ibba, M. 2006. Sticky end in protein synthesis. Nature 443, 41-42. (PDF)

Sauerwald, A., Zhu, W., Major, T.A., Roy, H., Palioura, S., Jahn, D., Whitman, W.B., Yates, J.R. 3rd, Ibba, M. and Söll,D. 2005. RNA-dependent cysteine biosynthesis in archaea. Science 307, 1969-1972. (PDF)