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Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology, in Cambridge, UK, Thomas A. Steitz, of Yale University, New Haven, Connecticut, USA, and Ada E. Yonath, of the Weizmann Institute of Science, in Rehovot, Israel, are the joint recipients of the 2009 Nobel Prize for Chemistry "for studies of the structure and function of the ribosome". DNA is at the heart of life, it is the code that allows cells to divide and organisms to reproduce, but it is the cellular machinery of the ribosome that translates the genetic code into proteins, which in turn underpin all of biochemistry: the oxygen-transporting haemoglobin, the antibodies of the immune system, hormones such as insulin, the collagen of the skin, and enzymes that digest our food, and tens of thousands of other proteins in the body with their own function and form. Ramakrishnan, Steitz and Yonath spent many years working to get a clear picture of what the ribosome looks like at the atomic level using X-ray crystallography; no mean feat given that the ribosome contains hundreds of thousands of atoms. The ribosome, named for ribonucleic acid and from the Greek, soma, for body is itself comprised of a protein and RNA complex. It reads the information in messenger RNA created from the DNA blueprint in the cell's nucleus. Based upon this information, it makes proteins in the process of translation. It is during this translation that the DNA/RNA language becomes manifest in the substance of life. Understanding the innermost workings of the ribosome is not only important for a scientific understanding of life but also represents a practical target. Given that bacterial ribosomes are so very different from human ribosomes, finding small molecules that inhibit bacterial ribosomes represents one approach to the development of novel antibiotics for fighting bacterial infection. Indeed, this year's chemistry laureates have all generated 3D models showing how different antibiotics bind to the ribosome and drug discovery scientists are already using these develop new antibiotics. Science has known the very general structure of the ribosome since the early 1970s. However, it was the application of powerful XRD techniques and skilful manipulation of the ribosome in various complex crystalline forms during the late 1990s, early 2000s, that led to the Nobel-winning high resolution structures of this cellular entity down to the few angstrom level. All three of the 2009 chemistry laureates published their work almost simultaneously in 2000. First, Steitz published the 50S (large bacteria) subunit from the archaea, Haloarcula marismortui and soon after Yonath revealed the structure of the 30S subunit from Thermus thermophilus. Very soon after that, Ramakrishnan published a more detailed structure. In May 2001, other researchers began to build on those structures and reconstructed the entire T. thermophilus 70S particle at 5.5 angstrom resolution. In November 2005, the structure of the Escherichia coli 70S ribosome was published with 3.5 angstrom resolution XRD and just two weeks another team published details of a cryo-electron microscopy study showing the structure of the E. coli protein-conducting channel bound to a translating ribosome. This structure showed the ribosome during the transfer of a newly synthesized protein strand into the protein-conducting channel. With this burgeoning field of study well underway, the first structures of ribosomes complexed with tRNA and mRNA molecules were revealed in 2006. Two independent research teams had used XRD to solve these structures and showed the functional interactions and rearrangements at high resolution for the 70S ribosome-tRNA complex. Yet other complexes and active arrangements have been revealed since, all building on the initial findings of this year's Nobel chemists. The 2009 Prize represents the third of a trilogy that take us from Darwin's theory of natural selection and evolution to an understanding of life at the molecular level. It was Rosalind Franklyn's X-ray images of DNA that led to the 1962 Prize for James Watson, Francis Crick, and Maurice Wilkins and X-rays that showed Roger D. Kornberg (2006 laureate) how information is copied to the messenger RNA molecule. The X-rayed ribosome completes the trilogy in 2009.
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Ribosome
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