READ a textbook about protein synthesis and you might think we already know
all there is to know about it. But that simply isn鈥檛 the case, says Harry
Noller, who heads a lab at the University of California at Santa Cruz that has
become a major force in research into ribosomes, the RNA-protein complexes that
assemble proteins.
For example, what starts an amino acid, attached to its transfer RNA, on the
journey from the 鈥淎 site鈥濃�攊ts first stop on the ribosome鈥攖o the 鈥淧
site鈥�, where it becomes part of a growing protein chain? How does the ribosome
know it鈥檚 got the right amino acid? 鈥淲e really don鈥檛 have much of a clue,鈥� says
Noller.
The answers will come with a closer look at the three-dimensional structure
of ribosomes in action, Noller says. The first step is to generate improved
high-resolution images, chiefly using X-ray crystallography. Noller鈥檚 lab made
landmark progress in this area last September when it published the most
detailed images ever of bacterial ribosome complexes (Science, vol 285, p 2095).
The images have a resolution of less than 0.8 nanometres, about the width of an
atom. And the lab is still squeezing more detail out of the crystal. 鈥淚t鈥檚 just
coming much more strongly into focus,鈥� he says.
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Ribosomes have two subunits and, for the first time, Noller鈥檚 images revealed
RNA bridges between them. Every time a ribosome builds a protein chain, a series
of precisely synchronised steps must occur at points within the ribosome. Noller
thinks the bridges are the basis of a communication system that could solve the
coordination puzzle.
One pay-off from his research is in the fight against antibiotic resistance.
鈥淏acteria have figured out how to defeat antibiotics and so we have to figure
out how to fight back,鈥� he says. Some antibiotics already block bacterial
protein synthesis, many in ways researchers don鈥檛 yet understand. But every new
detail Noller finds gives drug designers a concrete target to aim at.
Static images of ribosomes are only the beginning. The long-term goal is a
movie of protein synthesis made from snapshots. That is now becoming possible,
Noller says. 鈥淭his thing has been a mystery for 3.5 billion years and now we鈥檙e
getting the first glimpses of it,鈥� he says. 鈥淚t鈥檚 sort of like the guy who
shined the flashlight into the tomb in Egypt for the first time. What is all
that stuff in there? We鈥檙e just now coming to grips with what we鈥檙e seeing.鈥�