LA JOLLA, CA December 9, 2009 Even small errors made by cells during protein production can have profound disease effects, and nature has developed ways to uncover these mistakes and correct them. Though in the case of one essential protein building blockthe amino acid alaninenature has been extra careful, developing not one, but two checkpoints in her effort to make sure that this component is used correctly.
Now, scientists at The Scripps Research Institute have discovered the chemical basis for why these extraordinary efforts are necessary. The work was published in the December 10, 2009 issue of the prestigious journal Nature.
"What is shown here with the 'serine paradox' is just the tip of the iceberg," said senior author Paul Schimmel, who is the Ernest and Jean Hahn Professor and Chair of Molecular Biology and Chemistry and a member of The Skaggs Institute for Chemical Biology at Scripps Research. "In the coming years, there will be an increasing awareness of the role of mistranslation in human diseases and of how nature has struggled to find solutions to attenuate mistranslation and its consequences."
Spelling with Amino Acids and Proofreading for Errors
As letters of the alphabet spell out words, when amino acids are linked to one another in a particular order they "spell out" proteins. When amino acids are put in the wrong order, "spelling errors" (mistranslations) occur, often with devastating consequences for the health of the organism.
Normally, small RNA molecules, called transfer RNAs (tRNAs), transport specific amino acids to the ribosomes, the protein factories of cells, so that amino acids can be added to their correct place in a growing chain. At the beginning of this process, 20 tRNA enzymes, one for each of the 20 common amino acids, select the proper amino acid to be transported by a tRNA and join them together.
However, as Senior Research Associate Min Guo of the Schi
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Scripps Research Institute