Image: M. YUSUPOV et al.; copyright Science PROTEIN FACTORIES in all cells, known as ribosomes, are revealing their secrets. New detailed images are showing how their two subunits (blue and gray) interact with each other and with tRNAs (red, orange, yellow).

Scientists in the genome race did not cross a finish line draped with the usual 10-foot-long yellow ribbon but rather one marked by a string of genetic code stretching on for miles. From there researchers have started on a new course, hurrying to learn how this expanse of DNA instructs our cells to assemble proteins. Central to the process are ribosomes. These tiny organelles crank out thousands of proteins needed to sustain life with remarkable efficiency. And two papers in Friday's issue of Science offer a wealth of new information about how they work¿and how antibiotics can foul their performance.

"As biologists we are fascinated by these results because of their fundamental importance in understanding how the genetic code gets translated into proteins," says Venki Ramakrishnan, head of the U.K. Medical Research Council Laboratory of Molecular Biology and lead author of one of the papers. "However, pharmaceutical and biotech companies are keenly interested because this research not only helps us to understand how many known antibiotics work but also helps us to understand the basis of certain kinds of resistance. This will hopefully allow us to design new antibiotics in the future that can overcome the growing worldwide problem of resistance."

The new results are the latest in a fast-paced series of advances biologists have made in creating ever-sharper images of the ribosome and its two main parts: a large subunit called 50S and a smaller subunit, 30S. These two lumps¿which together measure some 200 angstroms wide¿are linked by a series of bridges. Between them lie three distinct docking stations of sorts. Transfer RNA (tRNA), carrying the building blocks of proteins, or amino acids, move from one docking station to the next, as if on a conveyor belt. In the process they are compared with genetic instructions from the cell nucleus, or messenger RNA (mRNA). When the two match, the tRNA drops its load and the ribosome catalyzes a reaction fusing the amino acid onto a growing protein chain (see sidebar)

In 1999, Harry Noller of the University of California at Santa Cruz and his colleagues used x-ray crystallography in a novel way to produce pictures of the entire ribosome at a resolution of 7.8 angstroms. Then in August of last year, Peter Moore, Thomas Steitz and their colleagues at Yale University published an account of the ribosome's 50S subunit in even greater detail. Another group from the Max Planck Institute and the Weizman Institute, headed by Ada Yonath, has worked on the 30S subunit. Now Ramakrishnan's team reports on the structure of the 30S subunit bound to pieces of mRNA and tRNA resolved to 3.1 to 3.3 angstroms in the presence and absence of antibiotic. And Noller's team has come back with images of the entire ribosome¿also bound to both tRNA and mRNA¿at a resolution of 5.5 angstroms.

Ramakrishnan's work reveals for the first time the exact four parts the ribosome uses to make sure that the three base pairs on a tRNA (an anticodon) match up properly with three on an mRNA (a codon). This codon-anticodon link is crucial to guarantee that the proper protein gets made. The team found that two different residues¿A1492 and A1493¿ change shape and probe the geometry of codon-anticodon interaction to check that the first two base pairs are matched. The third pairing, they observed, is afforded more freedom, in support of Francis Crick's wobble hypothesis. This flexibility helps explain how a single anticodon can bind to more than one codon.

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