Center for Gene Regulation in Health and Disease (GRHD)

Anton Komar

Professor and Director of the Center for Gene Regulation in Health and Disease
SR 259

We are interested in investigation of protein synthesis, co-translational protein folding and translational control of gene expression in eukaryotic cells.

Research in the laboratory has several major foci:

We are interested in the mechanistic aspect(s) of protein synthesis and translational control of gene expression in eukaryotic cells. We, in particular, aim to understand the evolutionary complexity of the eukaryotic (yeast) ribosome by studying the structure and function of several yeast ribosomal proteins (S5, S16 and others). Although ribosomal proteins are not involved in the catalysis of peptide bond formation, they do participate in a variety of activities in the translation process, such as the recruitment of tRNAs, translation factors and specific mRNAs. Eukaryotic ribosomes have evolved to be structurally more complex than those of prokaryotes and it is believed that this complexity is directly related to the evolution of the translation apparatus, appearance of new translation factors as well as appearance of multiple sophisticated translation control mechanisms, absent in prokaryotic cells. One of the key features differentiating eukaryotic (yeast) from prokaryotic ribosomes is the extent of protein-protein interactions on the ribosome surface; however, the significance of these interactions is unknown. We aim to uncover the significance of these interactions.

The research in the laboratory is further devoted to the investigation of the co-translational protein folding and the impact of synonymous mutations on gene function and phenotype. The journey of nascent polypeptides from synthesis at the peptidyl transferase center of the ribosome to full function involves multiple interactions, constraints, modifications and folding events. Each step of this journey impacts the ultimate expression level and functional capacity of the translated protein. It has become clear that the kinetics of protein translation is predominantly modulated by synonymous codon usage along the mRNA, and that this provides an active mechanism for coordinating the synthesis, maturation and folding of nascent polypeptides. We aim to understand how and at what step of the protein expression, translation elongation rates affect protein folding in the cell.


  • Nishant
    Dr. Nishant Singh
    Post-doctoral Fellow
    SR 258
  • Dr. Sujata Jha
    Presently a post-doctoral fellow at Northwestern University Feinberg School of Medicine
  • Dr. Arnab Ghosh
    Presently a post-doctoral fellow at at University of Missouri, Columbia
  • SupriyaJ
    Supriya Jindal
    PhD Student
    SR 258
  • Amra Ismail
    PhD Student
    SR 258
  • Puja Nanavaty
    PhD Student
    SR 258
  • Bryce
    Bryce J Waldal
    Rotating PhD Student
    SR 258
  • Artyom
    Artyom Kojukhov
    MS student
    SR 258

Complete List of Published Work in MyBibliography

Representative publications:

Krasheninnikov I.A., Komar A.A. and Adzhubei I.A. (1991) Nonuniform size distribution of nascent globin peptides, evidence for pause localization sites, and a cotranslational protein-folding model. J. Prot. Chem., 10, 445-454.

Komar A.A., Kommer A., Krasheninnikov I.A. and Spirin A.S. (1993) Cotranslational heme binding to nascent globin chains. FEBS Letters, 326, 261-263.

Komar A.A. and Jaenicke R. (1995) Kinetics of translation of gamma-B crystallin and its circularly permutated variant in an in vitro cell-free system: possible relations to codon distribution and protein folding. FEBS Letters, 376, 195-198.

Komar A.A., Kommer A., Krasheninnikov I.A. and Spirin A.S. (1997) Cotranslational folding of globin. J. Biol. Chem., 272, 10646-10651.

Komar A.A., Lesnik T. and Reiss C. (1999) Synonymous codon substitutions affect ribosome traffic and protein folding during in vitro translation. FEBS Letters, 462, 387-391.

Thual C., Komar A.A., Bousset L., Fernandez-Bellot E., Cullin C. and Melki R (1999) Structural characterization of Saccharomyces cerevisiae prion-like protein Ure2. J. Biol. Chem., 274, 13666-13614.

Komar A.A., Lesnik T., Cullin C., Merrick W.C., Trachsel H. and Altmann M. (2003) Internal initiation drives the synthesis of Ure2 protein lacking the prion domain and affects [URE3] propagation in yeast cells. EMBO J., 22, 1199-1209.

Komar A.A., Gross S., Barth-Baus D., Strachan R., Hensold J.O., Kinzy T. and Merrick W.C. (2005) Novel characteristics of the biological properties of the yeast Saccharomyces cerevisae initiation factor eIF2A J. Biol. Chem. 280, 15601-15611.

Komar A.A. and Hatzoglou M. (2005) Internal Ribosome Entry Sites in cellular mRNAs: Mystery of their existence. J. Biol. Chem. 280, 23425-23428.

Komar A.A. (2007) SNPs, Silent But Not Invisible, Science, 315, 466-467.

Komar A.A. (2007) Silent SNPs; impact on gene function and phenotype, Pharmacogenomics, 8, 1075-1080.

Galkin O., Bentley A.A., Gupta S., Toth B-A., Mazumder B., Kinzy T.G. Merrick W.C., Hatzoglou M., Pestova T.V., Hellen C.U.T. and Komar, A.A. (2007) Possible roles of the negatively charged N-terminal extension of Saccharomyces cerevisiae ribosomal protein S5 revealed by characterization of a yeast strain containing human ribosomal protein S5. RNA, 13, 2116-2128.

Pisareva VP, Pisarev AV, Komar AA, Hellen CUT, Pestova TV (2008) Efficient translation initiation on mammalian mRNAs with structured 5'-UTRs requires DExH-box protein DHX29. Cell, 135, 1237-1250.

Komar AA (2009) A pause for thought along the co-translational folding pathway. Trends Biochem. Sci. 34, 16-24.

Lumsden T, Bentley AA, Beutler W, Ghosh A, Galkin O, and Komar AA (2010) Yeast strains with N-terminally truncated ribosomal protein S5; implications for the evolution, structure and function of the Rps5/Rps7 proteins. Nucleic Acids Res. 38, 1261-1272.

Skabkin M.A., Skabkina O.V., Dhote V., Komar A.A., Hellen C.U. and Pestova TV. (2010) Activities of Ligatin and MCT-1/DENR in eukaryotic translation initiation and ribosomal recycling. Genes Dev. 24, 1787-1801.

Gasparian A.V., Neznanov N., Jha. S., Galkin O., Moran J.J., Gudkov A.V., Gurova K.V., and Komar A.A. (2010) Inhibition of EMCV and poliovirus replication by quinacrine: implications for the design and discovery of novel anti-viral drugs. J. Virol. 18, 9390-9397.

Komar, A.A. and Hatzoglou, M. (2011) Cellular IRES-mediated translation: the war of ITAFs in pathophysiological states. Cell Cycle, 10, 229-240.

Jha, S. and Komar, A.A. (2011) Birth, life and death of nascent polypeptide chains, Biotechnol. J., 6, 623-640.

Komar, A.A. Mazumder, B, and Merrick, WC. (2012) A New Framework for Understanding IRES-mediated translation. Gene 502, 75-86.

Bentley, A.A. Merkulov, S.M., Peng, Y., Rozmarynowycz, R., Qi, X., Pusztai-Carey, M., Merrick, W.C., Yee, V., McCrae, K.R., and Komar, A.A. (2012) Chimeric glutathione S-transferases containing inserts of kininogen peptides: potential novel protein therapeutics. J. Biol. Chem. 287, 22142-22150.

Hamasaki-Katagiri, N., Salari, R., Simhadri, V.L., Tseng, S.C., Needlman, E., Edwards, N.C., Sauna, Z.E. Grigoryan, V., Komar, A.A., Przytycka, T.M. and Kimchi-Sarfaty, C. (2012) Analysis of F9 point mutations and their correlation to severity of hemophilia B disease. Hemophilia B, 1-8.

Jha, S. and Komar, A.A. (2012) Using SecM arrest sequence as a tool to isolate ribosome bound polypeptides. J. Vis Exp. 64, 4027.

Edwards, N.C., Perry, A., Blaisdell, A., Kopelman, D.B. Fathke, R. Plum, W., Newell, J., Allen, C.E., Geetha S., Shapiro, A., Okunji, C., Kosti, I., Shomron, N., Grigoryan, V., Sauna, Z.E., Mandel-Gutfreund, Y., Komar, A.A. and Kimchi-Sarfaty, C. (2012). Characterization of coding synonymous and non-synonymous polymorphisms in ADAMTS13 using ex vivo and in silico approaches. PloS One. 7, e38864.

Jha, S. and Komar, A.A. (2012) Isolation of ribosome bound nascent polypeptides in vitro to identify translational pause sites along mRNA. J. Vis Exp. 65, 4026.

Shaltouki, A., Harford T., Komar, A.A. and Weyman, C.M. (2013) IRES-mediated translation of the pro-apoptotic Bcl2 family member PUMA, Translation, 1, e24391.

Das, P., Basu, A., Biswas, A., Poddar, P., Andrews, J., Barik, S., Komar, A.A. and Mazumder, B. (2013) Insights into the mechanism of ribosomal incorporation of mammalian L13a protein during ribosome biogenesis. Mol. Cell Biol, 33, 2829-2842.

Gartner JJ, Parker SC, Prickett TD, Dutton-Regester K, Stitzel ML, Lin JC, Davis S, Simhadri VL, Jha S, Katagiri N, Gotea V, Teer JK, Wei X, Morken MA, Bhanot UK; NISC Comparative Sequencing Program, Chen G, Elnitski LL, Davies MA, Gershenwald JE, Carter H, Karchin R, Robinson W, Robinson S, Rosenberg SA, Collins FS, Parmigiani G, Komar AA, Kimchi-Sarfaty C, Hayward NK, Margulies EH, Samuels Y. (2013) Whole-genome sequencing identifies a recurrent functional synonymous mutation in melanoma. Proc Natl Acad Sci U S A, 110, 13481-13486.

Hamasaki-Katagiri N, Salari R, Wu A, Qi Y, Schiller T, Filiberto AC, Schisterman EF, Komar AA, Przytycka TM, Kimchi-Sarfaty C. (2013) A gene-specific method for predicting hemophilia-causing point mutations. J Mol Biol., 425, 4023-4033.

Simhadri VL, Hamasaki-Katagiri N, Tseng SC, Bentley AA, Zichel R, Hershko AY, Komar AA, Kimchi-Sarfaty C. (2014) Factor IX oligomerization underlies reduced activity upon disruption of physiological conditions. Haemophilia, 20, e157-163.

Ghosh A, Jindal S, Bentley AA, Hinnebusch AG, Komar AA. (2014) Rps5-Rps16 communication is essential for efficient translation initiation in yeast S. cerevisiae. Nucleic Acids Res., 42, 8537-8555.
Ghosh A, Komar, A.A. (2015) Eukaryote-specific extensions in ribosomal proteins of the small subunit: structure and function. Translation. 3, 1, e999576.