Getting one's protein in a bunch -- When quality control fails in cells

COLUMBUS, Ohio -- Over time, a relatively minor mistake in protein production at the cellular level may lead to serious neurological diseases.

But exactly how the cell avoids such mistakes has remained unclear until now. Researchers at Ohio State University found the mechanism that prevents such errors, and explain their findings in the Proceedings of the National Academy of Sciences.

"Cells normally make a certain amount of mutant proteins, and use a series of degradation and recycling steps to get rid of them," said Michael Ibba, the study's lead author and an associate professor of microbiology at Ohio State University.

"But sometimes the cell produces more mutations than it can handle. That buildup can overwhelm the cell's ability to eliminate these mutants."

Left unchecked, these errors result in the buildup of faulty proteins within the cell. This buildup happens during translation, a process that cells use to make usable proteins. Over time, the researchers believe that the accumulated proteins might cause neurological diseases, such as Alzheimer's and Parkinson's.

Scientists know that cells use many enzymes to carry out translation properly. The enzymes that make the building blocks for translation carefully check for errors before proteins are made. If they find an error, they instruct the cell to destroy these building blocks, which are called aminoacyl-tRNAs. Cells break down these aminoacyl-tRNAs through a process called hydrolysis, in which one compound is split into other compounds in a reaction that uses water.

Ibba and his team work with a special family of enzymes called the aminoacyl-tRNA synthetases. These enzymes select the amino acids inside the cell that are used for producing proteins.

Ibba and his colleagues used a specific synthetase, phenylalanyl-tRNA synthetase, to investigate what happens when the wrong amino acid is selected. They carried out their experiments in a

Contact: Michael Ibba
Ohio State University

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