Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

18.01.2007
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 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!
Further information:
http://www.osu.edu

Further reports about: Error Protein Translation aminoacyl-tRNA hydrolysis

More articles from Life Sciences:

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

nachricht Party discipline for jumping genes
22.09.2017 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Party discipline for jumping genes

22.09.2017 | Life Sciences

The pyrenoid is a carbon-fixing liquid droplet

22.09.2017 | Life Sciences

Comet or asteroid? Hubble discovers that a unique object is a binary

21.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>