The Ribosome: Perfectionist Protein-Maker Trashes Errors
ScienceDaily (Jan. 9, 2009) — The enzyme machine that translates a cell's DNA code into the proteins of life is nothing if not an editorial perfectionist.
The ribosome, a perfectionist protein-maker, in all its majesty. Translation is what the ribosome does: it translates our genetic code to manufacture proteins which, as workhorses of the cell, carry out the business of life. (Credit: Image courtesy of Johns Hopkins Medical Institutions)
It turns out, the Johns Hopkins researchers say, that the ribosome exerts far tighter quality control than anyone ever suspected over its precious protein products which, as workhorses of the cell, carry out the very business of life.
"What we now know is that in the event of miscoding, the ribosome cuts the bond and aborts the protein-in-progress, end of story," says Rachel Green, a Howard Hughes Medical Institute investigator and professor of molecular biology and genetics in the Johns Hopkins University School of Medicine. "There's no second chance." Previously, Green says, molecular biologists thought the ribosome tightly managed its actions only prior to the actual incorporation of the next building block by being super-selective about which chemical ingredients it allows to enter the process.
Because a protein's chemical "shape" dictates its function, mistakes in translating assembly codes can be toxic to cells, resulting in the misfolding of proteins often associated with neurodegenerative conditions. Working with bacterial ribosomes, Green and her team watched them react to lab-induced chemical errors and were surprised to see that the protein-manufacturing process didn't proceed as usual, getting past the error and continuing its "walk" along the DNA's protein-encoding genetic messages.
"We thought that once the mistake was made, it would have just gone on to make the next bond and the next," Green says. "But instead, we noticed that one mistake on the ribosomal assembly line begets another, and it's this compounding of errors that leads to the partially finished protein being tossed into the cellular trash," she adds.
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Quality control by the ribosome following peptide bond formation
Hani S. Zaher1 & Rachel Green1
Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Correspondence to: Rachel Green1 Correspondence and requests for materials should be addressed to R.G. (Email: ragreen@jhmi.edu).
Abstract
The overall fidelity of protein synthesis has been thought to rely on the combined accuracy of two basic processes: the aminoacylation of transfer RNAs with their cognate amino acid by the aminoacyl-tRNA synthetases, and the selection of cognate aminoacyl-tRNAs by the ribosome in cooperation with the GTPase elongation factor EF-Tu. These two processes, which together ensure the specific acceptance of a correctly charged cognate tRNA into the aminoacyl (A) site, operate before peptide bond formation. Here we report the identification of an additional mechanism that contributes to high fidelity protein synthesis after peptidyl transfer, using a well-defined in vitro bacterial translation system. In this retrospective quality control step, the incorporation of an amino acid from a non-cognate tRNA into the growing polypeptide chain leads to a general loss of specificity in the A site of the ribosome, and thus to a propagation of errors that results in abortive termination of protein synthesis.
Source/Fonte: Nature
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COMENTÁRIO IMPERTINENTE DESTE BLOGGER:
Para os que estiverem pensando que, facilmente, uma molécula de RNA funcional saiu por aí codificando proteínas funcionais, uma ducha de água fria de Thomas A. Steitz, um mero ganhador de Prêmio Nobel:
