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The ribosome

As members of the Georgia Tech Center for Ribosomal Origins and Evolution
(RiboEvo), we are part of a team working to understand key steps in the
prebiotic processes that led to the modern ribosome, which catalyzes
the translation of mRNA into proteins. We hypothesize that, prior to the
development of the genetic code, the ribosome was preceded by a small
molecular complex that had weak, nonspecific catalytic abilities. We call this putative complex the "ancestral ribosome" (a-ribosome).

Our work on the a-ribosome is motivated by an analysis of the crystal structure of the large ribosomal subunit carried out in the laboratory of Loren Williams (School of Chemistry and Biochemistry, Georgia Tech), in which it was argued that the LSU evolved from the peptidyl transferase center outward. This work led to the recognition of bidentate RNA-magnesium clamps, in which a magnesium ion is chelated by two successive phosphate groups along the RNA backbone. Quantum calculations by Anton Petrov, a postdoc in the Harvey laboratory, have revealed the basis for the special role of magnesium in RNA chemistry (Petrov et al. (2011) RNA 17:291-297).

The Harvey Group is developing three-dimensional models for the ancestral ribosome. These efforts build on our previous studies on the "minimal ribosome." The first phase of that work was a collaboration with Robin Gutell, who had noted that organellar ribosomal RNAs are much smaller than rRNAs associated with cytoplasmic ribosomes. We examined the consequences of the large deletions in three-dimensional space and published a model for the minimal ribosome. Shortly after that, in collaboration with Rajendra Agrawal, we incorporated data from cryo-electron microscopy to develop a more complete (and more accurate) model for the Bos taurus mitochondrial ribosome.

We are examining the structure of fragments of ribosomal RNAs (and other RNAs) in vitro. As just one example, we have recently shown that Domain III of the 23S ribosomal RNA constitutes an independent folding unit. The isolated Domain III RNA folds to the native secondary structure in solution, and, when magnesium is added to the solution, many of the tertiary interactions that are seen in the intact ribosome also occur for the RNA free in solution. This paper has just been accepted by RNA (doi:10.1261/RNA.030692.111).