The 2009 Nobel Prize in Chemistry will be split among three researchers who, over the course of the past two decades, puzzled out—at the atomic level—the function of the ribosome in piecing together proteins.
The prize will be equally split between biophysicist Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology in Cambridge in England, biochemist Thomas Steitz of Yale University and molecular biologist Ada Yonath of the Weizmann Institute of Science in Rehovot, Israel, for their work in using x-ray crystallography to get a precise, atomic-scale map of the ribosome—the protein-making machine in all cells with nuclei that makes life possible.
"Rapid and accurate protein-making is essential to life," said molecular biologist Mans Ehrenberg of Uppsala University in explaining the award at a press briefing in Stockholm. "What the prize is all about is structure models of the ribosome at resolutions so high that you can see the atomic detail of the ribosome."
The key to that is x-ray crystallography in which x-rays are shone through a crystal filled with ribosomes, creating a scatter pattern that reveals their inner workings (detected by CCDs, the inventors of which were honored yesterday with the 2009 Nobel in Physics). Yonath showed this was possible by building crystals filled with ribosomes from heat-loving bacteria and salt-loving archaea as well as stabilizing the crystals by putting them at very-low temperatures.
Steitz then made the first high-resolution images of the ribosome in 1998, refining the technique until it reached the level of atomic detail. Ramakrishnan further revealed that the ribosome ensures accuracy not only by monitoring the stability of the bonds between amino acids that the ribosome stitches together into proteins but also by using a ruler to check the geometry of the bonds. "You get orders of magnitude higher accuracy," Ehrenberg explains, or one error for every 100,000 amino acids stitched.
This marks the second time in four years that the chemistry Nobel has been awarded to someone working with x-ray crystallography; in 2006 Roger Kornberg took the prize for detailing the structure of messenger RNA, which is the molecule that carries the information the ribosome uses to build proteins, such as insulin or hemoglobin. And, although the ribosome is clearly in the realm of biology, its workings are pure chemistry, says chemist Thomas Lane, president of the American Chemical Society. "This is an opportunity to remind people that truly anything you can see, touch, taste or smell that is made up of molecules falls into the domain of chemistry."
Yonath is just the fourth woman ever to win the Nobel Prize for Chemistry and the first since 1964 when Dorothy Hodgkin won for her x-ray crystallography work with penicillin and cholesterol. "In the U.S., half of the degrees in chemistry are going to young women," Lane says. Yonath's prize "is a powerful signal."
In addition to unraveling one of the key processes that makes life possible, the work also enables the detailed atomic study of how antibiotics work. Roughly half of all antibiotics attack pathogens' ribosomes, so understanding how the drugs fit into and disturb ribosomes' proper functioning could enable the discovery of new antibiotics to help stem the tide of rising antibiotic resistant strains.
"When I started this research [in the 1970s] I understood that I am going into a very important question in life," Yonath said via telephone during the announcement. She was reached at her daughter's home in Israel where she was spending the day with her granddaughter. "Now we are looking at bond after bond and [might find] new antibiotics. And it's very important because the resistance is growing and more and more antibiotics become less useful and less helpful."
Unraveling the Ribosome: Chemistry Nobel Awarded to Modelers of Cells' Protein-Maker [Update]
Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath first determined how to image the ribosome, then revealed how it does its protein-making work