Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new wrinkle in evolution -- Man-made proteins

23.05.2007
Nature, through the trial and error of evolution, has discovered a vast diversity of life from what can only presumed to have been a primordial pool of building blocks.

Inspired by this success, a new Biodesign Institute research team, led by John Chaput, is now trying to mimic the process of Darwinian evolution in the laboratory by evolving new proteins from scratch. Using new tricks of molecular biology, Chaput and co-workers have evolved several new proteins in a fraction of the 3 billion years it took nature.

Their most recent results, published in the May 23rd edition of the journal PLoS ONE, have led to some surprisingly new lessons on how to optimize proteins which have never existed in nature before, in a process they call ‘synthetic evolution.’

"The goal of our research is to understand certain fundamental questions regarding the origin and evolution of proteins," said Chaput, a researcher in the institute’s Center for BioOptical Nanotechnology and assistant professor in Arizona State University’s department of chemistry and biochemistry. "Would proteins that we evolve in the lab look like proteins we see today in nature or do they look totally different from the set of proteins nature ultimately chose" By gaining a better understanding of these questions, we hope to one day create new tailor-made catalysts that can be used as therapeutics in molecular medicine or biocatalysts in biotechnology."

... more about:
»ATP »Chaput »Evolution »Stability »amino acid »parent

The building blocks of proteins are 20 different amino acids that are strung together and folded to make the unique globular shape, stability and function of every protein. The mixing and matching of the amino acid chain like numbers in the lottery are what favor the odds in nature of finding just the right combinations to help generate biological diversity. Yet no one can predict how the string of amino acids sequence folds to make the 3-D functional structure of a protein.

To select the raw ingredients to create the proteins, Chaput’s group (which includes Harvard collaborator Jack Szostak, and ASU colleagues Jim Allen, Meitian Wang, Matthew Rosenow and Matthew Smith) began their quest by further evolving a protein that had been previously selected from a pool of random sequences.

Jack Szostak and Anthony Keefe first made the parental protein in 2001. To achieve their feat, they stacked the odds of finding just one or two new proteins and generated a library of random amino acid sequences so vast — 400 trillion — that it dwarfs the number of items in the entire Library of Congress (134 million).

They started with a small protein stretch 80 amino acids long. This basic protein segment acts as a protein scaffold that can be selected for the ability to strongly clutch its target molecule, ATP.

There was only one problem, the parental protein could bind ATP, but it wasn’t very stable without it.

"It turns out that protein stability is a major problem in biology," said Chaput. "As many as half of the 30,000 genes discovered from the human genome project contain proteins that we really don’t know what their structure is or whether or not they would be stable. So for our goal, we wanted to learn more about the evolution of protein folding and stability."

Chaput’s group decided to speed up protein evolution once again by randomly mutating the parental sequence with a selection specically designed to improve protein stability. The team upped the ante and added increasing amounts of a salt, guanidine hydrochloride, making it harder for the protein fragment to bind its target (only the top 10 percent of strongest ATP binders remained). After subjecting the protein fragments to several rounds of this selective environmental pressure, only the ‘survival of the fittest’ ATP binding protein fragments remained.

The remaining fragments were identified and amino acid sequences compared with one another. Surprisingly, Chaput had bested nature’s designs, as the test tube derived protein was not only stable, but could bind ATP twice as tight as anything nature had come up with before.

To understand how this information is encoded in a protein sequence, Chaput and colleagues solved the 3-D crystal structures for their evolutionary optimized protein, termed DX, and the parent sequence.

In a surprising result, just two amino acids changes in the protein sequence were found to enhance the binding, solubility and heat stability. "We were shocked, because when we compared the crystal structures of the parent sequence to the DX sequence, we didn’t see any significant changes," said Chaput. "Yet no one could have predicted that these two amino acids changes would improve the function of the DX protein compared to the parent.

The results have helped provide a new understanding of how subtle amino acid changes contribute to the protein folding and stability. Chaput’s team has developed the technology potential to take any of nature’s proteins and further improve its stability and function. "We have the distinct advantage over nature of being able to freeze the evolution of our lab-evolved proteins at different time points to begin to tease apart this random process and relate it to the final protein function," said Chaput.

Next, Chaput plans on further expanding his efforts to evolve proteins with new therapeutic features or catalytic functions.

Joe Caspermeyer | EurekAlert!
Further information:
http://www.asu.edu
http://www.biodesign.asu.edu

Further reports about: ATP Chaput Evolution Stability amino acid parent

More articles from Life Sciences:

nachricht Polymers Based on Boron?
18.01.2018 | Julius-Maximilians-Universität Würzburg

nachricht Bioengineered soft microfibers improve T-cell production
18.01.2018 | Columbia University School of Engineering and Applied Science

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

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

Polymers Based on Boron?

18.01.2018 | Life Sciences

Bioengineered soft microfibers improve T-cell production

18.01.2018 | Life Sciences

World’s oldest known oxygen oasis discovered

18.01.2018 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>