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
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
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.”
“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 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 reports about: > Biomechanics > Caetano-Anollés > HITS > Illinois River Watershed > Molecular Target > Protein > algorithm > building block > complex structure > computational method > multicellular organism > protein folding > protein structure > speed|scan atlineCT-System > three-dimensional structure > volumes of data
Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden
The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
22.09.2017 | Life Sciences
22.09.2017 | Medical Engineering
22.09.2017 | Physics and Astronomy