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 More than just a mechanical barrier – epithelial cells actively combat the flu virus
04.05.2016 | Helmholtz-Zentrum für Infektionsforschung

nachricht Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Nuclear Pores Captured on Film

Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.

Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...

Im Focus: 2+1 is Not Always 3 - In the microworld unity is not always strength

If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”

In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...

Im Focus: Tiny microbots that can clean up water

Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.

Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...

Im Focus: ORNL researchers discover new state of water molecule

Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.

In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...

Im Focus: Bionic Lightweight Design researchers of the Alfred Wegener Institute at Hannover Messe 2016

Honeycomb structures as the basic building block for industrial applications presented using holo pyramid

Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

The “AC21 International Forum 2016” is About to Begin

27.04.2016 | Event News

Soft switching combines efficiency and improved electro-magnetic compatibility

15.04.2016 | Event News

Grid-Supportive Buildings Give Boost to Renewable Energy Integration

12.04.2016 | Event News

 
Latest News

New fabrication and thermo-optical tuning of whispering gallery microlasers

04.05.2016 | Physics and Astronomy

Introducing the disposable laser

04.05.2016 | Physics and Astronomy

A new vortex identification method for 3-D complex flow

04.05.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>