Robert A. Zimmermann

Professor of Biochemistry and Molecular Biology, University of Massachusetts

R. Zimmermann Biochemistry & Molecular Biology Website

Ph.D.: Massachusetts Institute of Technology
Postdoctoral Training: Harvard Medical School; University of Geneva
Honors: Helen Hay Whitney Foundation Fellowship; National Institutes of Health Research Career Development Award; University Faculty Fellowship

Structure and Function of Ribosomes in Protein Synthesis

The central interests of my laboratory lie in the structure, function, and evolution of ribosomes, the organelles that carry out protein synthesis in all living cells.

One of our primary goal is to identify components of the ribosome that are in close proximity to tRNA molecules at the aminoacyl- (A), peptidyl- (P) and exit (E) sites. This is accomplished through the formation of short-range cross-links (2-4 Å) from tRNAs into which photoreactive azido- and thionucleotides have been introduced by in vitro transcription or recombinant RNA techniques. In particular, we are using this approach to define the contacts that tRNAs make with specific
nucleotide and amino acid sequences at the peptidyl transferase center of the 50S ribosomal subunit, and to investigate the conjunction of tRNA, mRNA and 16S rRNA at the decoding site of the 30S ribosomal subunit. The results fit well with recent high-resolution ribosome structures derived by crystallography and help to explain a number of the molecular interactions that occur between ribosomes and their ligands.

A second project entails an examination of the structural features of protein and RNA molecules that are involved in specific protein-RNA interaction. Our work here is focused on the binding of ribosomal protein S8 to 16S rRNA, and of protein L1 to 23S rRNA. We have recently defined "minimal" RNA binding sites of about 30 nucleotides for each of the proteins. The corresponding protein-RNA complexes are relatively simple and amenable to a wide variety of experimental
approaches that include site-directed mutagenesis, cross-linking, nucleotide analog substitution and, in collaboration with other laboratories, NMR and X-ray crystallography. Specific interactions are being modeled in an effort to understand how the configurations of protein and RNA change as the molecules form a complex.

Representative publications:

Manuilov, A.V., Zbozien-Pacamaj, R., Hixson, S,S,. Zimmermann, R.A. (2005), New Photoreactive Derivatives of tRNA for Probing the Peptidyl Transferase Center of the Ribosome RNA , in preparation.

Nevskaya, N., Tishchenko, S., Volchkov, S., Kljashtorny, V., Nikonova. E., Nikonov, O., Nikulin, A., Piendl, W., Zimmermann, R., Garber, M., and Nikonov, S. (2005), New Insights into the Interaction of Ribosomal Protein L1 with RNA, J. Mol. Biol. , under revision.

Maguire, B.A., Beniaminov, A.D. Ramu, P., Mankin, A.S. & Zimmermann, R.A. (2005), A Protein Component at the Heart of an RNA Machine: The Importance of Protein L27 for the Function of the Bacterial Ribosome, Molecular Cell , Nov 11;20(3):427-35.

Lavrik, I.N., Sergiev, P.V., Bogdanov, A.A., Zimmermann, R. A. & Dontsova, O.A. (2004), Escherichia coli Ribosomes as a Model for Testing New Photoactivated tRNA Analogs Containing 6-Thioguanosine Residues, Molecular Biology 38 , 937-944.

Zimmermann, R.A. (2003), The Double Life of Ribosomal Proteins, Cell 115, 130-132.

Nikulin, A., Eliseikina, I., Tishchenko, S., Nevskaya, N., Davydova, N., Platonova, O., Piendl, W., Selmer, M., Liljas, A., Drygin, D., Zimmermann, R., Garber, M. & Nikonov, S. (2003), Structure of the L1 Protuberance in the Ribosome, Nature Struct. Biol. 10, 104-108.

Kirillov, S.V., Wower, J., Hixson, S.S. and Zimmermann, R.A. (2002), Transit of tRNA through the Escherichia coli Ribosome: Cross-linking the 3' End of tRNA to Ribosomal Proteins at the P and E Sites, FEBS Lett. 514, 60-66.

Maguire, B.A., Manuilov, A.V. and Zimmermann, R.A. (2001), Differential Effects of Replacing Escherichia coli Ribosomal protein L27 with Its Homologue from Aquifex aeolicus , J. Bact . 183 , 6565-6572.

Maguire, B.A. and Zimmermann, R.A. (2001), The Ribosome in Focus. Cell 104, 813-816.

Drygin, D. and Zimmermann, R.A. (2000), Magnesium Ions Mediate Contacts between Phosphoryl Oxygens at Positions 2122 and 2176 of the 23S rRNA and Ribosomal Protein L1. RNA 6, 1714-1726.

Wower, J., Kirillov, S.V., Wower, I.K., Guven, S., Hixson, S.S. & Zimmermann, R.A. (2000), Transit of tRNA through the Escherichia coli Ribosome: Cross-linking of the 3' End of tRNA to Specific Nucleotides of the 23S Ribosomal RNA at the A, P and E Sites. J. Biol. Chem. 275, 37887-37894.

Zimmermann, R.A., Alimov, I., Uma, K., Wu, H., Wower, I., Nikonowicz, E.P., Drygin, D., Dong, P. & Jiang, L. (2000), How Ribosomal Proteins and rRNA Recognize One Another. In: The Ribosome: Structure, Function, Antibiotics, and Cellular Interactions (R.A. Garrett, S.R. Douthwaite, A. Liljas, A.T. Matheson, P.B. Moore & H.F. Noller, eds.), pp. 93-104. ASM Press, Washington, D.C.

Wower, I.K., Wower, J. and Zimmermann, R.A. (1998) Ribosomal Protein L27 Participates in Both 50S Subunit Assembly and the Peptidyl Transferase Reaction. J. Biol. Chem. 273, 19847-19852.

Zimmermann, R.A., Gait, M.J. and Moore, M.J. (1998) Incorporation of Modified Nucleotides into RNA for Studies on RNA Structure, Function and Intermolecular Interactions. In: Modification and Editing of RNA, pp. 59-84. (H. Grosjean & R. Benne, eds.). ASM Press, Washington, D.C.

Kalurachchi, K., Uma, K., Zimmermann, R.A. and Nikonowicz, E.P. (1997) Structural Features of the Binding Site for Ribosomal Protein S8 in Escherichia coli 16S rRNA Defined Using NMR Spectroscopy. Proc. Natl. Acad. Sci. USA 94, 2139-2144.

O’Connor, M., Thomas, C.L., Zimmermann, R.A. and Dahlberg, A.E. (1997) Decoding Fidelity at the Ribosomal A and P Sites: Influence of Mutations in Three Different Regions of the Decoding Domain in 16S rRNA. Nucleic Acids Res. 25, 1185-1193.

Rosen, K.V. and Zimmermann, R.A. (1997) Photoaffinity Labeling of 30S-Subunit Proteins S7 and S11 by 4-Thiouridine-substituted tRNAPhe Situated at the P Site of Escherichia coli Ribosomes. RNA 3, 1028-1036.