Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein origami: Quick folders are the best

31.01.2013
The evolutionary history of proteins shows that protein folding is an important factor. Especially the speed of protein folding plays a key role.

This was the result of a computer analysis carried out by researchers at the Heidelberg Institute for Theoretical Studies (HITS) and the University of Illinois at Urbana Champaign. For almost four billions of years, there has been a trend towards faster folding.


Nature has come up with numerous forms of protein folding. Most of these forms emerged after the biological Big Bang, which took place approximately 1.5 billion years ago. According to the study, folding speed belongs to the important factors of this diversification.
Image: Cedric Debes / HITS

“The reason might be that this makes proteins less susceptible to clumping, and that they can carry out their tasks faster,” says Dr. Frauke Gräter (HITS) who led the analysis. The results were now published in PLoS Computational Biology.

Proteins are elementary building blocks of life. They often perform vital functions. In order to become active, proteins have to fold into three-dimensional structures. Misfolding of proteins leads to diseases such as Alzheimer’s or Creutzfeld-Jakob. So which strategies did nature develop over the course of evolution to improve protein folding?

To examine this question, the chemist Dr. Frauke Gräter (Heidelberg Institute for Theoretical Studies) looked far back into the history of the Earth. Together with her colleague Prof. Gustavo Caetano-Anolles at the University of Illinois at Urbana-Champaign, she used computer analyses to examine the folding speed of all currently known proteins. The researchers have seen the following trend: For most of protein evolution, the folding speed increased, from archaea to multicellular organisms. However, 1.5 billion years ago, more complex structures emerged and caused a biological ‘Big Bang’. This has led to the development of slower-folding protein structures. Remarkably, the tendency towards higher speed in protein origami overall dominated, regardless of the length of amino acid chains constituting the proteins.

“The reason for higher folding speed might be that this makes proteins less susceptible to aggregation, so that they can carry out their tasks faster,” says Dr. Frauke Gräter, head of the Molecular Biomechanics research group at HITS.

Genetics and biophysics for large volumes of data

In their work, the researchers used an interdisciplinary approach combining genetics and biophysics. “It is the first analysis to combine all known protein structures and genomes with folding rates as a physical parameter,” says Dr. Gräter.

The analysis of 92,000 proteins and 989 genomes can only be tackled with computational methods. The group of Gustavo Caetano-Anolles, head of the Evolutionary Bioinformatics Laboratory at Urbana-Champaign, had originally classified most structurally known proteins from the Protein Database (PDB) according to age. For this study, Minglei Wang in his laboratory identified protein sequences in the genomes, which had the same folding structure as the known proteins. He then applied an algorithm to compare them to each other on a time scale. In this way, it is possible to determine which proteins became part of which organism and when. After that, Cedric Debes, a member of Dr. Gräter’s group, applied a mathematical model to predict the folding rate of proteins.

The individual folding steps differ in speed and can take from nanoseconds to minutes. No microscope or laser would be able to capture these different time scales for so many proteins. A computer simulation calculating all folding structures in all proteins would take centuries to run on a mainframe computer. This is why the researchers worked with a less data-intensive method. They calculated the folding speed of the single proteins using structures that have been previously determined in experiments: A protein always folds at the same points. If these points are far apart from each other, it takes longer to fold than if they lie close to each other. With the so-called Size-Modified Contact Order (SMCO), it is possible to predict how fast these points will meet and thus how fast the protein will fold, regardless of its length.

“Our results show that in the beginning there were proteins which could not fold very well,” Dr. Gräter summarizes. “Over time, nature improved protein folding so that eventually, more complex structures such as the many specialized proteins of humans were able to develop.”

Shorter and faster for evolution

Amino acid chains, which make up proteins, also became shorter over the course of evolution. This was another factor contributing to the increase in folding speed, as has been shown in the study.

“Since eukaryotes, i.e. organisms with a cell nucleus, emerged, protein folding became somewhat less crucial,” says Frauke Gräter. Since then, nature has developed a complex machinery to prevent and repair misfolded proteins. One example are the so-called chaperones. “It seems as if nature would accept a certain level of disorder in order to develop structures which could not have evolved otherwise.”

The number of known genomes and protein structures is continually increasing, thus expanding the data bases for further computer analyses of protein evolution. Frauke Gräter says “With future analyses of protein evolution, it might be possible for us to answer the related question whether proteins became more stable or more flexible over their billion-year-long history of evolution.”

The study was supported by the Klaus Tschira Foundation and the National Science Foundation of the US.
Scientific publication:
Debès C, Wang M, Caetano-Anollés G, Gräter F (2013) Evolutionary Optimization of Protein Folding. PLoS Comput Biol 9(1): e1002861. doi:10.1371/journal.pcbi.1002861
URL: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002861

Press contact:
Dr. Peter Saueressig
Public Relations
Heidelberg Institute for Theoretical Studies (HITS)
Tel: +49-6221-533-245
peter.saueressig@h-its.org

Scientific Contact:
Dr. Frauke Gräter
Molecular Biomechanics group
Heidelberg Institute for Theoretical Studies (HITS)
Tel: +49-6221-533-267
frauke.graeter@h-its.org

Prof. Dr. Gustavo Caetano-Anollés
Evolutionary Bioinformatics Laboratory
Dep. Of Crop Sciences, University of Illinois at Urbana-Champaign
332 National Soybean Res Ctr, 1101 West Peabody Drive
Urbana, IL 61801
+1 (217) 333-8172
gca@illinois.edu
http://cropsci.illinois.edu/directory/gca
HITS
HITS (Heidelberg Institute for Theoretical Studies) is a private, non-profit research institute. As a research institute of the Klaus Tschira Foundation, HITS conducts basic research from astrophysics to cell biology, with a focus on processing and structuring large volumes of data. The institute is jointly managed by Klaus Tschira and Andreas Reuter.

Evolutionary Bioinformatics Laboratory, University of Illinois at Urbana-Champaign

The Evolutionary Bioinformatics Laboratory at the University of Illinois focuses on creative ways to mine, visualize and integrate data from structural and functional genomic research, with a special focus on evolution of macromolecular structure and networks in biology.

Dr. Peter Saueressig | idw
Further information:
http://www.h-its.org
http://www.h-its.org/english/press/pressreleases.php?we_objectID=951
http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002861

More articles from Life Sciences:

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers shoot for success with simulations of laser pulse-material interactions

29.03.2017 | Materials Sciences

Igniting a solar flare in the corona with lower-atmosphere kindling

29.03.2017 | Physics and Astronomy

As sea level rises, much of Honolulu and Waikiki vulnerable to groundwater inundation

29.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>