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Scripps Research team uncovers chemical basis for extra 'quality control' in protein production
Date:12/9/2009

mmel-Yang lab, who is first author of the new paper, noted, "Sometimes there are mistakes. Where there is supposed to be alanine, there is a serine or glycine instead."

In 2006, the Schimmel-Yang lab contributed to research led by the Ackerman group at Jackson Laboratories that showed the consequences of this particular mistake in protein building for a strain of mutant mice. When the enzyme that adds the amino acid alanine to tRNAscalled alanyl-tRNA synthetase (AlaRS)mischarges its tRNA (tRNA Ala), the error leads to the accumulation of misfolded proteins and the mice display severe neurological and other defects. Another study by the Schimmel-Yang lab showed that E. coli bacteria with a similar mutation become very sensitive to serine and glycine, dying when these amino acids (but not others) are added to the culture.

Clearly, nature has a vested interest in avoiding such costly errors.

In fact, the Schimmel-Yang group showed in a Nature and a Science paper published in January 2008 and August 2009, respectively, that nature plays it extra safe with the quality control of alanine in protein production. Alanine's tRNA synthetase, AlaRS, not only loads the tRNA with an amino acid, but also checks to make sure it attached the right one. In addition, many organisms, from bacteria to humans, have an extra freestanding "spellchecker" moleculein the form of a protein called AlaXpto ensure that alanine is not confused with other amino acids.

"The editing function is redundant," said Guo. "This leads to several questions: Why are the cells so sensitive to alanine mistakes in particular? Why did AlaXps evolve so early? And why are redundant proteins still present that you supposedly don't need?"

A Case of Mistaken Identity

In the new Nature paper, the scientists used a variety of techniques, including x-ray cryatallography and kinetic and mutational analysis, to answer these questions.

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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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