Researchers watch protein unfolding in real-time with X-ray solution scattering
DOI: 10.1063/10.0002035
Researchers watch protein unfolding in real-time with X-ray solution scattering lead image
The way a protein folds, the 3D structure to which it conforms, is crucial to its biological function. Incorrectly folded proteins are believed to cause several diseases including Parkinson’s disease and Alzheimer’s disease. However, while fully understanding the dynamics of the folding process is important to many scientific fields, observing protein unfolding in real time and in solution has proved to be challenging.
Henry et al. shows how X-ray solution scattering could be used to observe the structural changes during the unfolding of the protein apomyoglobin. They found three separate states the protein undergoes while unfolding. These states defined as the native, the molten globule, and the unfolded state.
“By the method that we use to perform time-resolved X-ray solution scattering measurements, it is possible to detect minute changes to the scattering pattern, possibly revealing the structural changes with a great detail,” said author Oskar Berntsson.
To bias the apomyoglobin toward unfolding, the scientists used a laser pulse to trigger a rise in the protein’s temperature. They analyzed their collected data by using molecular dynamics simulations, in combination with ensemble optimization, which revealed more information about the structure. Their investigation revealed apomyoglobin is in a mixture between the native and molten globular state even before the temperature changes.
Berntsson hopes scientists will use similar strategies to analyze the structural changes of other proteins in solutions.
“I am currently involved in setting up and commissioning a setup for time-resolved X-ray solution scattering at the CoSAXS beamline at the Swedish synchrotron MAX IV, where users can perform experiments similar to the one we did.”
Source: “Real-time tracking of protein unfolding with time-resolved X-ray solution scattering,” by L. Henry, M. R. Panman, L. Isaksson, E. Claesson, I. Kosheleva, R. Henning, S. Westenhoff, and O. Berntsson, Structural Dynamics (2020). The article can be accessed at https://doi.org/10.1063/4.0000013 .
