Ribosome Begins to Unravel

Scientists had long thought that unraveling the structure of the ribosome, the cell's protein factory, would be as hard as climbing Mount Everest. A conglomerate of some 54 different proteins and three RNAs, the ribosome lacks the symmetry and repetitions that helped solve the structures of bigger objects, such as viruses. But now, they have at least set up a base camp. In this week's issue of Nature, scientists report having worked out the rough outlines of the ribosome's two subunits. Because of the low resolution, about 5 angstroms, their images are still too fuzzy for atomic detail, but they do show the overall arrangement of the proteins with respect to the RNAs--enough to make it a milestone, colleagues say.

A team led by biochemist Venki Ramakrishnan, who has just moved to the Medical Research Council Laboratory of Molecular Biology in Cambridge, U.K., tackled the smaller of the two subunits, called 30S, from the bacterium Thermus thermophilus. It took 2 years of tinkering to get the material they needed--good crystals with heavy atoms inserted as landmarks for inferring shapes from patterns of x-rays diffracted by atoms within the crystals. In the end, the detail was sufficient to reveal certain key features, such as where the RNA had looped back on itself to form a double helix and where the amino acids of the proteins formed distinctive spirals called a helices.

Meanwhile, crystallographer Thomas Steitz and biophysical chemist Peter Moore of Yale University and their colleagues focused on the structure of the larger, 50S subunit obtained from a salt-loving microbe, Haloarcula marismortui. Researchers had crystallized this subunit some 20 years ago but had been unable to generate detailed x-ray diffraction data. Moore and Steitz found that one obstacle may have been that the giant molecule tends to make twinned crystals. They were able to overcome this by rejecting the large majority of the crystals they made.

For years, ribosome experts have had to make do with indirect approaches to studying the ribosome's structure, such as mutating the various components to see how the changes affect protein synthesis. With the new structures, says Joachim Frank, a physicist at the New York State Department of Health Wadsworth Center in Albany, "we can now begin to put all the bits and pieces together."

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