Kurt Fredrick

fredrick.5@osu.edu

B.A., Biology, Gustavus Adolphus College
Ph.D., Microbiology, Cornell University
Postdoc, University of California Santa Cruz

Associate Professor of Microbiology
Member, Center for RNA Biology
Member, MCDB
Member, OSBP

Mechanistic studies of protein biosynthesis

Our group is interested in how the ribosome works. The ribosome is a large (~2.5 MDa), two-subunit, RNA-based machine that translates the genetic code in all organisms. In recent years, numerous structures of the ribosome and various ribosomal complexes have been determined by x-ray crystallography and cryo-electron microscopy. Today, a primary challenge for the field is to determine the functional roles of specific structural elements of the ribosome. Since the ribosome is the most common target of natural antibiotics, gaining a better understanding of how the ribosome functions may contribute substantially to the development of new antibiotics.

To address questions of ribosome structure and function, we use a combination of classical and site-directed mutagenesis. Interesting ribosomal and tRNA mutations are characterized in vivo and in vitro to help elucidate the molecular mechanisms that underlie translation. Students who join the lab will become familiar with bacterial genetics and ribosome biochemistry. To learn more about specific research projects in the lab, please see our recent publications.

Shoji S, Abdi NM, Bundschuh R, Fredrick K. Contribution of ribosomal residues to P-site tRNA binding. Nucleic Acids Res. 2009 Jul;37(12):4033-42.

Ling J, So BR, Yadavalli SS, Roy H, Shoji S, Fredrick K, Musier-Forsyth K, Ibba M. Resampling and editing of mischarged tRNA prior to translation elongation. Mol Cell. 2009 Mar 13;33(5):654-60.

Shoji S, Walker SE, Fredrick K. Ribosomal Translocation: One Step Closer to the Molecular Mechanism. ACS Chem Biol. 2009 Jan 27.

Qin D, Fredrick K.Control of translation initiation involves a factor-induced rearrangement of helix 44 of 16S ribosomal RNA. Mol Microbiol. 2009 Mar;71(5):1239-49.

Walker, S. E., Shoji, S., Pan, D., Cooperman, B. S. and K. Fredrick. 2008. Role of hybrid tRNA-binding states in ribosomal translocation. PNAS 105, 9192-9197.

Borovinskaya, M. A., Shoji, S., Fredrick, K. and J. H. Cate. 2008. Structural basis for hygromycin B inhibition of protein biosynthesis. RNA 14, 1590-1599.

Walker, S. E. and K. Fredrick. 2007. Preparation and evaluation of acylated tRNAs. Methods 44, 81-86.

Qin, D., Abdi, N. M. and K. Fredrick. 2007. Characterization of 16S rRNA mutations that decrease the fidelity of translation initiation. RNA 13, 2348-2355.

Ling, J., Roy, H., Qin, D., Rubio, M. T., Alfonzo, J. D., Fredrick, K. and M. Ibba. 2007. Pathogenic mechanism of a human mitochondrial tRNA Phe mutation associated with myoclonic epilepsy with ragged red fibers syndrome. PNAS 104, 15299-15304.

Borovinskaya, M. A., Shoji, S., Holton, J. M., Fredrick, K., and J. H. D. Cate. 2007. A steric block in translation caused by the antibiotic spectinomycin. ACS Chem Biol 2, 545-552.

Shoji, S., Walker, S. E. and K. Fredrick. 2006. Reverse translocation of tRNA in the ribosome. Mol Cell 24, 931-942.

Tram, U., Fredrick, K., Werren, J. H. and W. Sullivan. 2006. Paternal chromosome segregation during the first mitotic division determines Wolbachia-induced cytoplasmic incompatibility. J Cell Sci 119, 3655-3663.

Walker, S. E. and K. Fredrick. 2006. Recognition and positioning of mRNA in the ribosome by tRNAs with expanded anticodons. J Mol Biol 360, 559-609.

McGarry, K. G., Walker, S. E., Wang, H. and K. Fredrick. 2005. Destabilization of the P site codon-anticodon helix results from movement of tRNA into the P/E hybrid state within the ribosome. Mol Cell 20, 613-622.

Abdi, N. M. and K. Fredrick. 2005. Contribution of 16S rRNA nucleotides forming the 30S subunit A and P sites to translation in E. coli . RNA 11, 1624-1632.

Yassin, A., Fredrick, K. and A. S. Mankin. 2005. Deleterious mutations in small subunit ribosomal RNA identify functional sites and potential targets for antibiotics. PNAS 102, 16620-16625.

Hoang, L., Fredrick, K. and H. F. Noller. 2004. Creating ribosomes with an all-RNA 30S subunit P site. PNAS 101, 12439-12443.

Fredrick, K. and H. F. Noller. 2003. Catalysis of ribosomal translocation by sparsomycin. Science 300, 1159-1162.

Fredrick, K. and H. F. Noller. 2002. Accurate translocation of mRNA by the ribosome requires a peptidyl group or its analog on the tRNA moving into the 30S P site. Mol Cell 9, 1125-1131.