University of Rochester
Department of Biology
River Campus Box 270211
Rochester, New York 14627-0211
MC 3-8555 (office)
MC 3-8560 (lab)
(585) 275-3704 (office)
(585) 273-3321 (lab)
We study the mechanism of protein synthesis using ensemble
and single molecule fluorescent methods. The ribosome is a
central component of cell metabolism, an extremely complex
and highly dynamic machine. We are interested to learn how
structural dynamics of the ribosome and ribosomal ligands
enable protein synthesis.
During proteins synthesis, ribosomes move along mRNA.
This movement is coupled to translocation of tRNAs inside
of the ribosome. It has been discovered that translocation
requires ratchet-like intersubunit rotation. We are trying
to understand the mechanics of this ratchet mechanism.
There are other types of ribosome movements besides codon-by-codon translocation, such as programmed frame-shifting, ribosome shunting on poly-cistronic mRNAs and ribosome scanning during initiation of protein synthesis in eukaryotes. We are expanding our research toward investigation of molecular mechanism of these specialized translocation events.
We are currently addressing following questions:
- How does the catalyst of ribosomal translocation, elongation factor G, rectify spontaneous intersubunit movement into unidirectional translocation of the ribosome?
- What is the mechanism of programmed ribosome frame-shifting and bypassing segments of mRNA?
- How do elongation factor G and ribosome recycling factor (RRF) disassemble ribosome into subunits after termination of protein synthesis?
- 2011. mRNA translocation occurs during the second step of ribosomal intersubunit rotation. Nat Struct Mol Biol. 18,457-62.
- 2009. Following movement of the L1 stalk between three functional states in single ribosomes. Proceedings of the National Academy of Sciences USA. 106, 2571-2576.
- 2008. Structural dynamics of the ribosome. Current Opinion In Chemical Biology. 12, 674-683.
- 2008. Spontaneous intersubunit rotation in single ribosomes. Molecular Cel. 30, 578-588(† these authors contributed equally to this work).
- 2007. Elongation factor G stabilizes the hybrid-state conformation of the 70S ribosome. RNA. 13, 1473-1482.
- 2007. The antibiotic viomycin traps the ribosome in an intermediate state of translocation. Nature Structural and Molecular Biology. 14, 493-497(† these authors contributed equally to this work).
- 2007. Observation of intersubunit movement of the ribosome in solution using FRET. Journal of Molecular Biology. 370, 530-540.