蛋白质合成的关键步骤

Scientists at the University of California, Santa Cruz, have trapped the ribosome（核糖体）, a protein-building molecular machine essential to all life, in a key transitional state that has long eluded（逃避） researchers. Now, for the first time, scientists can see how the ribosome performs the precise mechanical movements needed to translate genetic code into proteins without making mistakes. "This is something that the whole field has been pursuing for the past decade," said Harry Noller, Sinsheimer Professor of Molecular Biology at UC Santa Cruz. "We've trapped the ribosome in the middle of its movement during translocation（易位，迁移）, which is the most interesting, profound, and complex thing the ribosome does."

Understanding ribosomes is important not only because of their crucial role as the protein factories of all living cells, but also because many antibiotics work by targeting bacterial ribosomes. Research on ribosomes by Noller and others has led to the development of novel antibiotics that hold promise for use against drug-resistant bacteria.

Noller's lab is known for its pioneering work to elucidate（阐明） the atomic structure of the ribosome, which is made of long chains of RNA and proteins interlaced（交错） together in complicated foldings. Using x-ray crystallography, his group has shown the ribosome in different conformations as it interacts with other molecules. The new study, led by postdoctoral researcher Jie Zhou, is published in the June 28 issue of Science.

To make a new protein, the genetic instructions are first copied from the DNA sequence of a gene to a messenger RNA molecule. The ribosome then "reads" the sequence on the messenger RNA, matching each three-letter "codon" of genetic code with a specific protein building block, one of 20 amino acids. In this way, the ribosome builds a protein molecule with the exact sequence of amino acids specified by the gene. The matching of codons to amino acids is done via transfer RNA molecules, each of which carries a specific amino acid to the ribosome and lines it up with the matching codon on the messenger RNA.

"The big question has been to understand how messenger RNA and transfer RNA are moved synchronously through the ribosome as the messenger RNA is translated into protein," Noller said. "The transfer RNAs are large macromolecules, and the ribosome has moving parts that enable it to move them through quickly and accurately at a rate of 20 per second."

The key step, called translocation, occurs after the bond is formed joining a new amino acid to the growing protein chain. The transfer RNA then leaves that amino acid behind and moves to the next site on the ribosome, along with a synchronous movement of the messenger RNA to bring the next codon and its associated amino acid into position for bond formation. The new study shows the ribosome in the midst of a key step in this process.

"This gives us snapshots of the intermediate state in the movement," Noller said. "We can now see how the ribosome does this with a rotational movement of the small subunit, and we can see what look to be the 'pawls' of a ratcheting mechanism that prevents slippage of the translational reading frame."