Ribosomes Reveal Their RNA Secrets

Ribosomes, the cell’s protein factories, have been tough targets for researchers aiming to see them close up. Now, for the first time on the atomic scale, scientists know what most of the ribosome looks like.

The large ribosomal subunit shows RNA (gray), proteins (gold), and a molecule in the active site (green at center). Nenad Ban et al./Science

A new map reveals most of the structures of the two RNA molecules and 31 proteins that make up the larger of the two subunits of a bacterial ribosome. The map suggests where and how the ribosome chemically stitches amino acids into a protein.

The new details confirm suspicions that ribosomes’ RNA molecules, and not their proteins, make peptides. That result adds to evidence that an RNA-based biochemistry preceded today’s DNA-based biology (SN: 8/10/96, p. 93). The results also will help researchers tease out further details of the ribosome’s structure and function, information that may be useful in the design of new antibiotics.

For decades, the ribosome’s unwieldy size has made it a challenge to study. Yet in recent years, researchers around the world have produced maps of increasingly higher resolution using a battery of tools—X-ray crystallography, electron microscopy, and computers.

“It has taken a long time to get the [ribosome] crystals to the point where everybody got them back in the corner and forced them to give up their secrets,” says Yale University’s Peter B. Moore, a member of the research team that published two papers on ribosome structure in the Aug. 11 Science.

Moore and his colleagues found that the proteins surround a convoluted RNA mass. The RNA appeared as expected, but many of the proteins didn’t, he says.

“In many places, the proteins give the impression of a man-of-war jellyfish,” he says. “Instead of being the compact globular structures that most proteins are, these things will often have a globular part and then there will be a little strand that extends deep into the structure of the ribosome.”

These novel protein structures appear to stabilize the ribosome, while the RNA assembles amino acids into peptide chains. The new map showed no proteins near the site where RNA seems to catalyze the protein-making reaction.

“It’s just RNA at the center,” comments Thomas R. Cech, president of the Howard Hughes Medical Institute in Chevy Chase, Md. “That’s pretty exciting.”

When the researchers introduced molecules presumed to dock at the location where peptide bonds form, they confirmed that the site lies at one end of a tunnel structure previously proposed to reside within the ribosome. The locations of those added molecules also hint that a particular adenine base on the RNA is necessary in creating the chemical bonds between peptides.

A different approach, published in the same issue of Science by a neighboring Yale team, led to the same conclusion. In experiments on the ribosome of a different bacterium, the team discovered an unusual acidity, which they hypothesized would indicate chemical activity. The group localized it to an adenine equivalent of the one described by Moore’s team.

“When we got that result, we were really excited,” says team member Scott A. Strobel. He then walked upstairs to Moore’s colleague, Thomas A. Steitz, and compared notes. “We realized that this altered acidity . . . was at the same nucleotide that their structure predicted was the active site.”

The new snapshot of the ribosome could focus ideas about the origin of life. Says Steitz, “I think it makes it clear that the first ribosome must have been made of all RNA.”

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