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 is to understand how the ribosome moves and how such dynamics govern the various steps of translation. Since the ribosome is the most common target of natural antibiotics, gaining insight on ribosome function may contribute substantially to the development of new antibiotics.
We use a combination of genetic, molecular, and biochemical methods to study protein synthesis in bacteria. Examples of questions under investigation in the laboratory include: (1) Which features of mRNA tune the rate of initiation? And how do the mechanisms of initiation compare among the different bacterial phyla? (2) How do rRNA dynamics contribute to the mechanism of decoding (aminoacyl-tRNA selection)? (3) What roles do nonessential ribosome-associated GTPases play in the cell?
Member, Center for RNA Biology
Liu, Q. and Fredrick, K. 2016. Intersubunit bridges of the bacterial ribosome. J. Mol. Biol. 428, 2146-2164.
Ying, L. and Fredrick, K. 2016. Epistasis analysis of 16S rRNA ram mutations helps define the conformational dynamics of the ribosome that influence decoding. RNA 22, 499-505.
Liu, Q. and Fredrick, K. 2015. Roles of helix H69 of 23S rRNA in translation initiation. Proc. Natl. Acad. Sci. U.S.A. 112, 11559-11564.
Fosso, M. Y., Zhu, H., Green, K. D., Garneau-Tsodikova, S., and Fredrick, K. 2015. Tobramycin variants with enhanced ribosome-targeting activity. ChemBioChem 16, 1565-1570.
Fredrick, K. 2015. Another look at mutations in ribosomal protein S4 lends strong support to the domain closure model. J. Bacteriol. 197, 1014-1016.
Balakrishnan, R., Oman, K., Shoji, S., Bundschuh, R., and Fredrick, K. 2014. The conserved GTPase LepA contributes mainly to translation initiation in Escherichia coli. Nucleic Acids Res. 42, 13370-13383.
McClory, S. P., Devaraj, A. and Fredrick, K. 2014. Distinct functional classes of ram mutations in 16S rRNA. RNA 20, 496-504.
Fagan, C. E., Dunkle, J. A., Maehigashi, T., Dang, M. N., Devaraj, A., Miles, S. J., Qin, D., Fredrick, K., and Dunham, C. M. 2013. Reorganization of an intersubunit bridge induced by disparate 16S ribosomal ambiguity mutations mimics an EF-Tu-bound state. Proc. Natl. Acad. Sci. U.S.A. 110, 9716-9721.
Liu, Q. and Fredrick, K. 2013. Contribution of intersubunit bridges to the energy barrier of ribosomal translocation. Nucleic Acids Res. 41, 565-574.
Qin, D., Liu, Q., Devaraj, A., and Fredrick, K. 2012. Role of helix 44 of 16S rRNA in the fidelity of translation initiation. RNA 18, 485-495.
Devaraj, A. and Fredrick, K. 2010. Short spacing between the Shine-Dalgarno sequence and P codon destabilizes codon-anticodon pairing in the P site to promote +1 programmed frameshifting. Mol. Micro 78, 1500-1509.
McClory, S. P., Leisring, J. M., Qin, D., and Fredrick, K. 2010. Missense suppressor mutations in 16S rRNA reveal the importance of helices h8 and h14 in aminoacyl-tRNA selection. RNA 16, 1925-1934.
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