Department of Biological, Geological, and Environmental Sciences (BGES)

Dr. Anton Komar
Dr. Anton A. Komar
Dr. Anton Komar
Associate Professor;
Ph.D., Moscow State University;
Office Phone: (216) 687-2516
Lab Phone: (216) 523-7259
e-mail: a.komar@csuohio.edu
COS Faculty Profile

Education:

B.S./M.S., Biochemistry/Molecular Biology, Moscow State University, 1985.

Ph.D., Molecular Biology, Moscow State University, 1991.

Research Interests:

Our research is concerned with protein synthesis, protein folding and translational control of gene expression in eukaryotic cells. Research in the laboratory has 3 major foci:

1. We are interested in protein structure/function relationships and the rational protein design. Proteins are constructed in many cases from a number of structurally and/or functionally conserved modules that are genetically mobile and used repeatedly in the course of evolution. These modules may be sufficiently large so as to constitute an entire protein domain or as small as a short peptide composed of a few amino acids. We are in interested in the design of chimeric proteins with novel properties.

2. A large body of work in the laboratory is concerned with the mechanism of protein synthesis and translational control of gene expression in eukaryotic cells. Recent studies have pointed to the key role of translational control in regulating gene expression during development, differentiation, cell cycle progression, cell growth, apoptosis, and stress. Regulation of translation is mainly exerted at the initiation step of protein synthesis, thus allowing rapid modification of the overall rate of translation as well as post-transcriptional regulation of gene expression due to changes in the relative selection of different mRNA species utilizing different mechanisms of translation initiation. Assembly of the 80S ribosome at a start codon within the majority of eukaryotic mRNAs involves recruitment of the 40S ribosome (and associated initiation factors) to the mRNA 5'-end followed by ribosome scanning (in search of the initiation codon). However, it was shown that some mRNAs can be translated via inter nal initiation, a process that is generally independent of the recognition of the 5'-mRNA end and involves direct recruitment of the 40S ribosome to the vicinity of the initiation codon (directed by internal ribosome entry site (IRES) elements). We are interested in the mechanism of the initiation of protein synthesis, the IRESs function and factors that affect IRESs activity. We are in particular interested in the structure and function of certain ribosomal proteins that may affect initiation of protein synthesis.

3. The research in the laboratory is further devoted to 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.

Books:

Komar A.A. editor (2009) Single Nucleotide Polymorphisms - Methods and Protocols, 2d edition. In "Methods in Molecular Biology", Springer/Humana Press, Totowa,NJ

Selected recent publications (in chronological order):

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.

Yaman I., Fernandez J., Liu H., Caprara M., Komar A.A., Koromilas A., Zhou L., Snider M., Scheuner D., Kaufman R.J. and Hatzoglou M. (2003) The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leader. Cell, 113, 519-531.

Fernandez J., Yaman I., Huang C., Liu H., Lopez A.B., Komar A.A., Caprara M., Merrick W.C. Snider M., Kaufman R.J., Lamers W.H. and Hatzoglou M. (2005) Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation. Mol. Cell, 17, 405-416.

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.

Kapasi, P., Chaudhuri, S, Vyas, K., Baus, D. Komar, A.A., Fox, P.L. Merrick, W.C. and Mazumder, B. (2007) L13a Blocks 48S Assembly: Role of a General Initiation Factor in mRNA-specific translational Control. Mol. Cell, 25, 113-126.

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, V.P., Pisarev, A.V., Komar, A.A. , Hellen, C.U.T. and Pestova, T.V. (2008) Efficient translation initiation on mammalian mRNAs with structured 5'-UTRs requires DExH-box protein DHX29. Cell, 135, 1237-1250.

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

Lumsden, T., Bentley, A.A., Beutler, W., Ghosh, A., Galkin, O. and Komar A.A. (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 T.V. (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.

Basu, A., Das, P., Chaudhuri, S., Bevilacqua, E., Andrews, J., Barik, S., Hatzoglou, M., Komar, A.A. and Mazumder B. (2011) Requirement of rRNA methylation for 80S ribosome assembly on a cohort of cellular Internal Ribosome Entry Sites. Mol. Cell Biol. 31, 4482-4499.

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.

Hershko, K., Simhadri, V., Blaisdell, A., Hunt, R., Newell, J., Tseng, S.C., Hershko, A.Y., Choi, J.W., Sauna, Z.E., Wu, A., Bram, R.J., Komar, A.A. and Kimchi-Sarfaty, C. (2012) Cyclosporin A Impairs the Secretion and Activity of ADAMTS13 (A Disintegrin and Metalloprotease with Thrombospondin Type 1 Repeat) J. Biol. Chem. 287, 44361-44371.

Komar, A.A. Taylor, D.J. and Merrick, W.C. (2013) Eukaryotic protein biosynthesis: The elongation cycle. In Encyclopedia of Biological Chemistry (Lennarz W.J. and Lane M. D., eds), Academic Press/Elsevier Science, Elsevier, Oxford, 2d edition.


Copyright © 2005
Department of Biological, Geological, and Environmental Sciences
College of Science, Cleveland State University
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Update: 26 September, 2005

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