Protein origami: Quick folders are the best

January 31, 2013
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. Credit: Cedric Debes / HITS


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 folding?

To examine this question, the chemist Dr. Frauke Gräter (Heidelberg Institute for ) 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 . 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.



"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


"Since eukaryotes, i.e. organisms with a cell nucleus, emerged, 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 , 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."

Explore further: Protein folding made easy

More information: Debes, C. et al. (2013) Evolutionary Optimization of Protein Folding. PLoS Comput Biol 9(1): e1002861. doi:10.1371/journal.pcbi.1002861

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