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 Grter (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 Grter, 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. Grter.
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 prot
|Contact: Peter Saueressig|
Heidelberg Institute for Theoretical Studies (HITS)