B.A. Biology, Gustavus Adolphus College, 1992
We are 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 X-ray crystal structures of the ribosome and its isolated subunits and many cryo-EM reconstitutions of functional ribosomal complexes have been reported. Today, a primary challenge for the field is to elucidate 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 should contribute substantially to the development of new antibiotics. In our group, we use mutagenesis and antibiotics to address questions of ribosome structure and function. One of our primary interests is translocation, the coupled movement of tRNA and mRNA within the ribosome. In recent work, we have shown that destabilization of the codon-anticodon helix accompanies movement of tRNA from the P/P to P/E state, an important transition during translocation.
|McGarry, K. G., Walker, S. E., Wang, H. and Fredrick, K. 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 Fredrick, K. 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.
Noller, H. F., Hoang, L. and Fredrick, K. 2005. The 30S ribosomal P site: A function of 16S rRNA. FEBS Letters 579: 855-858.
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.
Noller, H. F., Yusupov, M. M., Yusupova, G. Z., Baucom, A., Lieberman, K., Lancaster, L., Dallas, A., Fredrick, K., Earnest, T. N. and J. H. D. Cate. 2001. Structure of the ribosome at 5.5 � resolution and its interaction with functional ligands . Cold Spring Harbor Symp. Quant. Biol. 66: 57-66.
Fredrick, K., Dunny, G. M. and H. F. Noller. 2000. Tagging ribosomal protein S7 allows rapid identification of mutants defective in assembly and function of 30S subunits. J. Mol. Biol. 298: 379-394.