IMAGE: Researchers from Freiburg have been able to study the correct rate of signal movement over several time periods. view more
Credit: Graphic: Steffen Wolf
Think for a minute for a tree moving in the wind. How long does it take for a twig to reach the trunk of a tree? How is this movement transmitted through the tree? Researchers at the University of Freiburg are shifting this question to the analysis of proteins – which are molecular devices in cells. A team of researchers led by Dr. Dr. Thorsten Hugel from the Institute of Physical Chemistry, and Dr. Steffen Wolf and Dr. Dr. Gerhard Stock from the Institute of Physics studies how the signals that cause structural changes in proteins travel from one site to another. They are also trying to find out how fast these devices happen. Until now, researchers have not been able to study the exact rate of signal movement because it involves many time scales – ranging from nanoseconds to seconds. The researchers in Freiburg, however, have now achieved such a mission by combining various experiments, simulations, and theoretical studies. They publish their findings in the scientific journal Chemical Science.
Compared to trees, the trends for the protein studied in the study, Hsp90, appear on logarithmic time scales. All major movements take about ten times as long as the small, individual movements that make up the largest one. Wolf explains, “For example, a branch moves on a time scale of a second; the branch by ten seconds; and the stock by 100 seconds.” Using a combination of new experimental and theoretical methods- modern allowed the researchers to monitor allosteric communication, in other words, to show how the reaction process in Hsp90 altered a remote protein binding site. According to Stock, the team found a dynamic hierarchy that expands this allosteric process, which ranges from nanosecond to millisecond timeframes and length blades from picometers to several nanometers.
Furthermore, the reaction process in Hsp90 is accompanied by a structural change in the same amino acid Arg380. Arg380 then distributes structured information to a subdomain of the protein, and ultimately, delivers it to the protein as a whole. The change in structure closes the central binding site of the protein, thus allowing it to perform new functions. University of Freiburg researchers suspect that ranking mechanisms similar to those tested in Hsp90 proteins are also extremely important in signal movement within other proteins. Hugel says this could be useful for drug use to control proteins.
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The researchers who worked on the study are members of the Excellence Group – Center for Integrated Biological Identification Studies (CIBSS), the 1381 Collaborative Research Center “Dynamic Organization of Cellular Protein Machineries,” and Unit Research 5099 “Reducing the complexity of nonequilibrium systems,” which is supported by the German Research Foundation, DFG.
Original publication:
Wolf, S., Sohmen, B., Hellenkamp, B., Thurn, J., Stock, G., Hugel, T. (2021): Ranking dynamics in allostery after ATP hydrolysis studied with FRET measurements single molecules and MD simulations. In: Chemical Science. DOI: 10.1039 / D0SC06134D
Contact:
Professor Steffen Wolf and Prof. Dr. Gerhard Stock
Institute of Physics
Faculty of Mathematics and Physics
University of Freiburg
Phone .: 0761 / 203-5913
Email: [email protected]; [email protected]
Prof. Dr. Thorsten Hugel
Institute of Physical Chemistry
Faculty of Chemistry and Pharmacy
University of Freiburg
Phone .: 0761 / 203-6192
Email: [email protected]
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