The ribosome is a macromolecular machine made up of RNA and protein. Its function of converting genetic information into proteins is an essential step for all forms of life (see Figure 1).


Figure 1. How Genetic Information is Expressed in the Cell. This process is defined by two basic steps: transcription of DNA into RNA and translation of RNA into protein. Translation is performed by the ribosome. We are designing antibiotics to inhibit ribosome function and block protein synthesis, thereby killing and/or preventing the growth of the bacterial cell.

The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs (rRNAs). The 23S (grey, Figure 2) and the 5S rRNAs (light blue, top) associate with their respective proteins (royal blue) to make up the large subunit of the ribosome (left), while the 16S RNA (cyan) associates with its proteins (dark blue) to make up the small subunit (right).

Figure 2. The small and large subunits each contains part of a binding site for 3 transfer RNAs or tRNAs (red, orange, and yellow) to be positioned in the ribosome. You can see how the two subunits fit around the tRNAs in Figure 3. These tRNAs are the means by which genetic information is converted into protein.


Figure 3. The entire ribosome in its closed depiction (above) and in the "cracked open" depiction (below) exposing the tRNAs. [Image adapted from M Yusupov et al. (2001) Science, 293:883-896.]

How a ribosome works

A gene is a piece of DNA that contains the genetic code for a protein. By a process called transcription a copy of a gene can be made into RNA form, called a messenger RNA or mRNA. The mRNA is made up of information containing units called nucleotides and associates with the ribosome. Transformation of this information into proteins begins by decoding the nucleotides with the help of the tRNAs. The mRNA is translated using a genetic code comprised of 3 nucleotides per word or codon. Each codon corresponds to one of 21 specific amino acids (the building blocks of a protein). The tRNA molecules, with their cognate amino acids attached, interact with the small subunit of the ribosome and facilitate the decoding process. A portion of the tRNA also associates with the large subunit and positions the amino acid corresponding to the triplet codon in the peptidyl transferase center of the ribosome. Here the amino acids are linked like beads on a string to form a protein. This process is very much like translating text between two different languages. Ribosomes translate the information in the genetic code (where nucleotides are one set of letters and words in the mRNA) into the code of proteins (where amino acids make up a second set of letters and words).