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.

Roy, H. and Ibba, M. 2008. RNA-dependent lipid remodeling by bacterial multiple peptide resistance factors. Proceedings of the National Academy of Sciences USA. In Press

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

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.

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)

Prætorius-Ibba, M., Ataide, S., Hausmann, C., Levengood, J., Ling, J., Wang, S., Roy, H. and Ibba, M. 2006. Quality Control during aminoacyl-tRNA synthesis. Chemistry in Industry 55, 129-134. (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)

Ambrogelly, A., Frugier, M., Ibba, M., Söll, D. and Giegé, R. 2005. Transfer RNA recognition by class I lysyl-tRNA synthetase from the Lyme disease pathogen Borrelia burgdorferi.
FEBS Letters 579, 2629-2634.

Ibba, M., Francklyn, C., and Cusack, S., eds. 2005. The Aminoacyl- tRNA synthetases. Landes Bioscience, Georgetown, Texas.

Prætorius-Ibba, M., Rogers, T.E., Samson, R., Kelman, Z. and Ibba, M. 2005. Association between archaeal prolyl-and leucyl-tRNA synthetases enhances tRNAPro aminoacylation. Journal of Biological Chemistry 280, 26099-26104. (PDF).

Ataide, S.F., Jester, B.C., Devine, K.M. and Ibba, M. 2005. Stationary phase expression and aminoacylation of a tRNA-like small RNA. EMBO Reports 6, 742-747. (PDF).

Roy, H., Ling, J., Alfonzo, J.D. and Ibba, M. 2005. Loss of editing activity during the evolution of mitochondrial phenylalanyl-tRNA synthetase. Journal of Biological Chemistry 280, 38186-38192. (PDF)

Ibba, M., and Söll,D. 2004. Aminoacyl-tRNAs: setting the limits of the genetic code. Genes and Development 18, 731-738. (PDF)

Levengood, J.D., Ataide, S.F., Roy, H., and Ibba, M. 2004. Divergence in non-cognate amino acid recognition between class I and class II lysyl-tRNA synthetases. Journal of Biological Chemistry 279, 17707-17714. (PDF)

Bentin, T., Hamzavi, R., Salomonsson, J., Roy, H., Ibba, M., and Nielsen, P.E. 2004. Photoreactive bicyclic amino acids as substrates for mutant Escherichia coli phenylalanyl-tRNA synthetases. Journal of Biological Chemistry 279, 19839-19845. (PDF)

Ibba, M., and Francklyn, C. 2004. Turning tRNA upside down: when aminoacylation is not a prerequisite to protein synthesis. Proceedings of the National Academy of Sciences USA 101, 7493-7494. (PDF)

Korencic, D., Ahel, I., Schelert, J., Sacher, M., Ruan, B., Stathopoulos, C., Blum, P., Ibba, M., and Söll,D. 2004. A freestanding proofreading domain is required for protein synthesis quality control in Archaea. Proceedings of the National Academy of Sciences USA 101, 10260-10265. (PDF)

Ataide, S.F. and Ibba, M. 2004. Discrimination of cognate and non-cognate substrates at the active site of class II lysyl-tRNA synthetase. Biochemistry 43, 11836-11841 (PDF)

Roy, H., Ling, J., Irnov, and Ibba, M. 2004. Post-transfer editing in vitro and in vivo by the beta-subunit of phenylalanyl-tRNA synthetase. The EMBO Journal 23, 4639-4648 (PDF)

Mejlhede, N., Monthan, A., Theisen, M. and Ibba, M. 2003. Differentiation of Borrelia burgdorferi sensu lato strains using class I lysyl-tRNA synthetase encoding genes. Medical Microbiology and Immunology 192, 79-83.(Abstract) (PDF)

Prætorius-Ibba, M. and Ibba, M. 2003. Aminoacyl-tRNA synthesis in archaea: different but not unique. Molecular Microbiology 48, 631-637.(Abstract) (PDF)

Polycarpo,C., Ambrogelly,A., Ruan,B., Tumbula-Hansen,D., Ataide,S.F., Ishitani,R., Yokoyama,S., Nureki,O., Ibba, M., and Söll,D. 2003. Activation of the pyrrolysine suppressor tRNA requires formation of a ternary complex with class I and class II lysyl-tRNA synthetases. Molecular Cell 12, 287-294.(Abstract) (PDF)

Jester, B., Levengood, J., Roy, H., Ibba, M., and Devine, K. 2003. Non-orthologous replacement of lysyl-tRNA synthetase prevents addition of lysine analogs to the genetic code. Proceedings of the National Academy of Sciences USA 100, 14351-14356.(PDF)

Ahel, I., Korencic, D., Ibba, M., and Söll,D. 2003.Trans-editing of mischarged tRNAs. Proceedings of the National Academy of Sciences USA 100, 15422-15427.(PDF)

Terada, T., Nureki, O., Ishitani, R., Ambrogelly, A., Ibba, M., Söll D and Yokoyama S. 2002. Functional convergence of two lysyl-tRNA synthetases with unrelated topologies. Nature Structural Biology 9: 257-262. (Abstract) (PDF)

Ambrogelly, A., Korencic, D., and Ibba, M. 2002. Functional annotation of class I lysyl-tRNA synthetase phylogeny indicates a limited role for gene transfer. Journal of Bacteriology 184. 4954-4960.(Abstract) (PDF)

Pavlickova, P., Jensen, N.M., Paul, H., Schaeferling, M., Giammasi, C., Kruschina, M., Du, W.D., Theisen, M., Ibba, M., Ortigao, F. and Kambhampati, D. 2002. Antibody detection in human serum using a versatile protein chip platform constructed by applying nanoscale self-assembled architectures on gold. Journal of Proteome Research 1, 227-231.(Abstract) (PDF)

Ibba, M. 2001. Discriminating right from wrong. Science 294: 70-71.(Enhanced Perspective)