(Oct. 7th, 2009) Puzzling out the three-dimensional structure of the ribosome and the mechanistic details of the translation of genetic information into protein chains is an edifying example of excellent research. That’s one reason why Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath (see photo, from left) will now receive the Nobel Prize for Chemistry.
The Nobel Foundation's description for this award reads a like a thrilling race for structures with the highest resolution.
Back in the 1980s, Ada Yonath from the Israel’s Weizmann Institute of Science made significant contributions to obtaining the structure of the 50S ribosomal subunit with her crystals from the archaeon Haloarcola marismortui. A decade later, in 1998, Thomas Steitz and his collegues at Yale University used cryo-electron microscopy to obtain a low resolution (9 Å) structure of the 50S complex.
Just a year after this, in 1999, higher resolution structures (up to 4.5 Å) came in rapid succession from all three research groups. And another scientist, Harry Noller, who also was a good candidate for that Nobel prize, joined the club: he reported the structure of the 70S ribosome from Thermus thermophilus at 7.8 Å resolution, containing tRNAs in the ribosomal A, P and E sites and an mRNA in the track around the neck of the 30S subunit.
However, these structures neither revealed the complete atomic model nor the ribosome's innermost workings. In the last ten years, biochemical and new structural analysis have disclosed how the ribosome can both read codons correctly and discriminate the different tRNAs. Combining electron microscopy, NMR and X-ray crystallography together with intelligent biochemistry has finally provided explanations for how a ribosome correctly reads a codon and how it forms a peptide. Much of this work has come from the laboratory of Venkatraman Ramakrishnan at the MRC in Cambridge (UK).
Perhaps the most startling result of ribosome research was the realisation that the formation of new peptide bonds at the peptidyl-transferase centre was not catalysed by a protein but rather by ribosomal RNA. This research has also medical implications since there are antibiotics that work by perturbing the translation process in the ribosome. Hence, this knowledge can be put to a practical and immediate use for the development of new antibiotics.
Karin Hollricher