DNA gets all the glory, but genetic material wouldn’t be anywhere without ribosomes — cellular protein factories that build everything from insulin to fingernails. The Royal Swedish Academy of Sciences announced October 7 that three scientists will share the Nobel Prize in chemistry for unmasking the structure of the ribosome. The work enriched fundamental research on proteins, shed light on how life got going on Earth and is leading to the development of new antibiotics.
Ada Yonath of the Weizmann Institute of Science in Rehovot, Israel, shares the prize with Howard Hughes Medical Institute investigator Thomas Steitz of Yale University and Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology in Cambridge, England. The researchers will share equally the prize of 10 million Swedish kronor (1.42 million dollars).
By the 1960s, scientists had figured out that the instructions encoded in a cell’s DNA were transcribed into RNA. In cells with DNA sequestered in a nucleus, this messenger RNA, or mRNA, brings the instructions out of the nucleus into the cell’s cytoplasm (in bacteria and other non-nucleated cells, everything happens in the cytoplasm). Then ribosomes get to work. The two chunks of a ribosome, the large and small subunits, bind together, and with the help of other RNA molecules, the ribosome builds the specified proteins, be they hemoglobin or hair.
By the 1970s, scientists had a schematic of how genetic information got turned into proteins. But there was still much to learn about the ribosome. In pioneering work begun in the late 1970s, Yonath used X-ray crystallography to generate a rudimentary map of the ribosome of the bacterium Geobacillus stearothermophilus (she selected this hot spring bacterium because she thought it might have super stable ribosomes). With each refinement, Yonath got a more and more detailed look at the ribosome. By the mid 1990s other scientists, including Steitz and Ramakrishnan, were also zooming in on the cellular workhorse.
“We tried for a number of years.… It seemed to us a bit like trying to climb Mount Everest,” said Steitz during a press teleconference October 7. “We knew it was doable in principle, but we didn’t know whether we were going to be able to get there, and we didn’t know the route through which we should travel.”
In August and September of 2000, each of this year’s Laureates reached the destination, publishing super-high-resolution structures of the subunits of certain bacterial ribosomes, research with far-reaching implications, says Jeremy Berg, director of the National Institute of General Medical Sciences in Bethesda, Md.
Making proteins — the basic construction material of living things — is “absolutely fundamental to all biology,” says Berg. Scientists had been perplexed at how well ribosomes do their work: A single ribosome forms about 20 bonds per second to connect the protein building blocks. Yet ribosomes rarely make mistakes. Ramakrishnan’s work in particular elucidated how the ribosome’s smaller subunit uses a sort of molecular ruler to build each protein correctly. Using the ruler twice, the ribosome double checks each building block, resulting in an error rate of once per 100,000 building blocks.
Ribosome research also tackled a looming chicken-and-egg question, says Berg.
By the time the laureates began their research, the notion of an “RNA world,” in which ancient life existed as RNA before the invention of proteins and DNA, was already brewing. It turned out that ribosomes had something to say about it. For many years, proteins were recognized as the workhorses of life. But ribosomes, which make proteins, are also made of RNA, notes Berg. It was the work of Steitz in particular that revealed that the part of the ribosome doing the heavy lifting is mostly RNA, not protein. The research “completely supports the RNA world hypothesis,” says Berg.
Ribosomes are also good targets for developing antibiotics, mainly because of differences between human and bacterial ribosomes. Interfering with this protein-making machinery in bacteria has proved a successful strategy for bringing some of these disease-causing microbes to a standstill. Research by each of the winners has shown the way different antibiotics bind to the ribosome. For example, some antibiotics block the tunnel through which the growing protein exits the ribosome, while others prevent the formation of the bond between the protein building blocks. The antibiotic research continues today.
Not only was the research like tackling Mount Everest, the end result was similarly exciting, notes Steitz. Peering into the inner workings of the ribosome “was very exhilarating,” he says. “In fact, it was the most exhilarating moment I’ve had in science.”
