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 strain of E. coli bacteria cells.
They changed certain components of the translation process and found that the replacements halved hydrolysis, and in some cases reduce hydrolysis by as much as 90 percent. In other experiments, the researchers also slightly modified the protein. Further tests showed that this alteration left the modified enzymes incapable of preventing mistakes during protein production.
“It revealed an essential function for this group of enzymes in hydrolysis,” Ibba said.
In related work, Ibba and other researchers have found that bacteria grow poorly or die when this enzymatic step is missing.
“We knew it was an important process for the cell, but until this study, we didn't know exactly why it was so important,” Ibba said. “Other researchers have actually disrupted this process in mice, and found that it leads to neurodegenerative diseases resembling Alzheimer's and Parkinson's.”
Ibba and his team face more challenges. They want to know precisely how cells correct for these mistakes, and knowing this may give them insight to neurological diseases.
“The key to efficient cell growth is to limit the level of mistakes to a tolerable amount,” Ibba said. “In spite of all its checks and balances, a cell isn't perfect. Even though textbooks tell you that gene expression is flawless, this just isn't possible in real life.
“Ultimately – and it's a long way off – we hope to develop a way to therapeutically correct for these errors,” he said. “If we understand how these diseases start, and it relates to mistakes in the mechanism we studied, then there may be a means to try and correct these mistakes.”
Ibba conducted the study with Ohio State colleagues Jiqiang Ling, a graduate research associate in the Ohio State Biochemistry Program, and Hervé Roy, a postdoctoral researcher in microbiology.
This study was supported by a grant from the National Science Foundation.
Michael Ibba | EurekAlert!
Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology