Researchers find features that shape mechanical force during protein synthesis

March 4, 2019 by Matt Swayne, Pennsylvania State University
In this image, a protein (blue and black) is beginning to make its long (molecularly speaking) journey from the ribosome (red and yellow) through the tube and toward its eventual folding. Credit: PENN STATE

Like any assembly line, the body's protein-building process generates a mechanical force as it produces these important cellular building blocks. Now, a team of researchers suggest they are one step closer to understanding that force. They also built a mathematical model to help guide scientists with future investigations into how the body creates proteins.

"In the past five years, it has been found experimentally that when a self-assembles and folds into its three-dimensional structure during its synthesis, a can be generated that changes the speed of ," said Edward O'Brien, assistant professor of chemistry at Penn State and an Institute for CyberScience co-hire. "What was unknown until this study is what features of protein folding determine the strength of that mechanical force. It's important to understand such factors that influence the speed at which this machine works because the speed has been shown to determine protein function, structure and behavior in cells."

Proteins, which are used to make tissues, bones and muscles, are synthesized by the ribosome, a whose purpose is to convert the genetic information contained in messenger RNA, or mRNA, into a protein. The ribosome moves along a mRNA, reading the code it contains and adding links to the elongating protein chain, which exits the ribosome through a narrow tube. Eventually, this process stitches together an unfolded protein and, once it exits the tube, it begins the complex folding process that leads to its three-dimensional shape.

According to O'Brien, the shape—or topology—of the protein, and its stability, as well as the speed of translation, determine the mechanical force that the folding process generates. He added that the distance traveled by the nascent protein during the process is actually quite large, at least compared to the dimensions of the minute world of chemical reactions.

"As the protein is being synthesized, it emerges through a narrow channel, or tube, which is about 10 nanometers in length and 1.5 nanometers in diameter," said O'Brien. "The protein doesn't fold within that tube, but it begins to fold as the nascent chain emerges out of that tube. What's interesting to us, and to the community, is that this force is transmitted over 10 nanometers, which is long compared to molecular length scales. The length of a chemical bond, in comparison, is about .1 nanometers."

This mechanical force can then provide feedback and change the speed at which synthesis happens, said O'Brien.

Sarah Leininger, doctoral candidate in chemistry at Penn State and first author of the paper, said the team used considerable computer resources for the study, which was published online today (March 1) in the Proceedings of the National Academy of Sciences. She added that the team used about 5 million computer hours to get the results for the study and create simulations, which resemble movies, of the synthesis process.

O'Brien said that because of the amount of computational power needed to simulate the complexity of protein synthesis, the team used a that helped them make accurate approximations of the process.

"These simulations were primarily that allow us to model the evolution of the system over time," said O'Brien. "The key aspect of our model is we use coarse-grained simulations, where we don't represent every , but we approximate and describe groups of atoms, grouping them into one interaction site in our simulations. That lets us simulate longer time scales and be able to model this process that we wouldn't be able to model otherwise."

The simulations—and the equation devised by the researchers that describes the simulations—could help save time and money for scientists studying protein synthesis. Rather than conducting expensive experiments, or months-long simulations on a supercomputer, for example, scientists could perform calculations on a laptop computer in seconds.

"What this allows us to do—and other scientists to do—is without doing expensive simulations, without even doing experiments, they can reasonably estimate what will happen," said O'Brien.

Explore further: Mechanical force controls the speed of protein synthesis

More information: Sarah E. Leininger et al. Domain topology, stability, and translation speed determine mechanical force generation on the ribosome, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1813003116

Related Stories

Mechanical force controls the speed of protein synthesis

May 16, 2018

As cells create proteins, the proteins modulate synthesis speed by exerting a mechanical force on the molecular machine that makes them, according to a team of scientists who used a combination of computational and experimental ...

Maximum precision in protein synthesis

September 8, 2017

Researchers from the Center for Molecular Biology of Heidelberg University (ZMBH) and the German Cancer Research Center (DKFZ) have investigated the mode of action of a molecular chaperone vital to protein synthesis. Together ...

Simpler model gets to the point with proteins

June 6, 2018

Computational models have come a long way in their ability to simulate the most basic biological processes, such as how proteins fold. A new technique created by Rice University researchers should enable scientists to model ...

A molecular hammock for cotranslational modification

December 20, 2018

Proteins do most of the real work in cells and are modified in accordance with functional requirements. An LMU team has now shown how proteins are chemically altered on the ribosome, even before they fold into the active ...

New insights to the function of molecular chaperones

August 25, 2012

(Phys.org)—Heidelberg molecular biologists have gained new insights into the function of so-called molecular chaperones in protein synthesis. The team headed by Dr. Günter Kramer and Prof. Dr. Bernd Bukau of the DKFZ-ZMBH ...

Recommended for you

EPA adviser is promoting harmful ideas, scientists say

March 22, 2019

The Trump administration's reliance on industry-funded environmental specialists is again coming under fire, this time by researchers who say that Louis Anthony "Tony" Cox Jr., who leads a key Environmental Protection Agency ...

Coffee-based colloids for direct solar absorption

March 22, 2019

Solar energy is one of the most promising resources to help reduce fossil fuel consumption and mitigate greenhouse gas emissions to power a sustainable future. Devices presently in use to convert solar energy into thermal ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.