Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Proteins that can take the heat

31.03.2017

Proteins stable at high temperatures unfold more slowly than cold temperature counterparts

Ancient proteins may offer clues on how to engineer proteins that can withstand the high temperatures required in industrial applications, according to new research published in the Proceedings of the National Academy of Sciences. Researchers used experiments to examine critical differences between 15 proteins from the thioredoxin family, including seven extinct protein sequences that date back more than 4 billion years and were resurrected using ancestral sequence reconstructions.


Ancient proteins may offer clues on engineering proteins to withstand high temperatures required in industrial applications.

Credit: Rensselaer Polytechnic Institute

"In industrial applications, proteins could do some of the work of chemicals with less energy and less toxicity, but they have to be able to withstand the higher temperatures of industrial processes," said George Makhatadze, a Constellation Professor of Biocomputation and Bioinformatics and member of the Center for Biotechnology and Interdisciplinary Studies at Rensselaer Polytechnic Institute. "This research suggests that ancestral reconstruction methods can be used to design proteins that unfold more slowly, offering greater utility, at higher temperatures."

The experiments showed that the difference in stability between proteins from the same family is caused primarily by differences in the energy required to unfold the proteins, a finding that upholds a long-held theory known as the "principle of minimal frustration," proposed by physicists about 30 years ago.

Proteins are molecular chains in which each link is one of 20 amino acids. Once the chain is assembled, various forces along its length interact, causing the string to twist and turn, and ultimately fold into a three-dimensional shape. The protein can only perform its function when properly folded. Most proteins remain folded within a set range of temperature, pH, or pressure conditions, breaking down when subjected to conditions outside of these tolerances.

Not all the rules that govern protein folding are known, and Makhatadze wanted to understand how proteins within the same family, with similar structure, are able to perform the same life-sustaining function in vastly different thermal environments. Thioredoxins, for example, are present in all organisms, from those that live near boiling hydrothermal vents to frigid Arctic waters.

One known rule helps to explain why there are an astronomical number of sequences possible for proteins with hundreds and even thousands of links, but only a small subset of those possible sequences are found in nature. This rule, the principle of minimal frustration, posits that nature chooses only those sequences that fold most efficiently, reducing undesired interactions between amino acids and producing faster, less frustrated, folding patterns.

To be consistent with the principle of minimal frustration, Makhatadze said, proteins with similar structure but different thermodynamic stability should fold along the same efficient pattern, but those with greater ability to tolerate heat should take longer to unfold. Experiments, undertaken first with eight modern-day thioredoxins, proved the hypothesis correct.

"We tested the folding rates among thioredoxins, a family of proteins that perform the same function but -- because they function in different thermal conditions -- must be different in terms of thermodynamics," said Makhatadze. "And what we observed is that for these proteins, they indeed fold with the same rate, but they unfold with a different rate -- which is what we predicted."

In the next step, researchers tested extinct versions of thioredoxins that had been obtained using a technique called ancestral sequence reconstruction. The extinct versions unfolded more slowly than modern versions, in some case folding 3,000 times more slowly than a modern counterpart.

"Here we have two versions of a protein from the same family and one unfolded in seven seconds, the other in six hours," Makhatadze said. "That means you can get useful function from the protein for six hours versus seven seconds. This shows that ancestral sequence reconstruction may be a route to proteins that are more stable at high temperatures."

The finding is supported by previously published research and geochemical data which indicates that Earth and its oceans were hotter in the ancient past.

"Previous research supports the finding that older proteins are more stable, but this new research shows these ancient proteins are more stable because they unfold more slowly," Makhatadze said.

"Evidence for the principle of minimal frustration in the evolution of protein folding landscapes" can be found using the digital object identifier doi: 10.1073/pnas.1613892114. The research was supported by the National Science Foundation. Makhatadze was joined in the research by Fanco Tzul, a postdoctoral research associate, and graduate student Daniel Vasilchuk.

Makhatadze's research is enabled by the vision of The New Polytechnic, an emerging paradigm for higher education which recognizes that global challenges and opportunities are so great they cannot be adequately addressed by even the most talented person working alone. Rensselaer serves as a crossroads for collaboration -- working with partners across disciplines, sectors, and geographic regions -- to address complex global challenges, using the most advanced tools and technologies, many of which are developed at Rensselaer. Research at Rensselaer addresses some of the world's most pressing technological challenges -- from energy security and sustainable development to biotechnology and human health. The New Polytechnic is transformative in the global impact of research, in its innovative pedagogy, and in the lives of students at Rensselaer.

###

About Rensselaer Polytechnic Institute

Rensselaer Polytechnic Institute, founded in 1824, is America's first technological research university. For nearly 200 years, Rensselaer has been defining the scientific and technological advances of our world. Rensselaer faculty and alumni represent 85 members of the National Academy of Engineering, 17 members of the National Academy of Sciences, 25 members of the American Academy of Arts and Sciences, 8 members of the National Academy of Medicine, 8 members of the National Academy of Inventors, and 5 members of the National Inventors Hall of Fame, as well as 6 National Medal of Technology winners, 5 National Medal of Science winners, and a Nobel Prize winner in Physics. With 7,000 students and nearly 100,000 living alumni, Rensselaer is addressing the global challenges facing the 21st century--to change lives, to advance society, and to change the world. To learn more, go to http://www.rpi.edu.

Media Contact

Mary Martialay
martim12@rpi.edu

 @rpinews

http://news.rpi.edu/ 

 

Mary Martialay | EurekAlert!

More articles from Life Sciences:

nachricht Research team creates new possibilities for medicine and materials sciences
22.01.2018 | Humboldt-Universität zu Berlin

nachricht Saarland University bioinformaticians compute gene sequences inherited from each parent
22.01.2018 | Universität des Saarlandes

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>