Weill Cornell Medicine researchers have created a powerful new method for producing “movies” of evolving protein structures at speeds of up to 50 frames per second. This technique, developed by Senior author Dr. Simon Scheuring, allows for a better understanding of the structural changes that biological molecules undergo over time.Researchers in this area regularly capture detailed images of stationary proteins and other molecules with enough precision to see the positions of individual atoms. However, creating dynamic visualizations of molecular structures, essentially making movies, has been much more difficult. The primary author of the paper is Yining Jiang, a doctoral candidate at the Weill Cornell Graduate School of Biomedical Sciences.
In their research, published on April 17 in Nature Structural & Molecular Biology, the scientists utilized a relatively new method of measurement known as high-speed atomic-force microscopy (HS-AFM), which utilizes an extremely sensitive. The scientists have developed a new way to use a high-speed atomic force microscope (HS-AFM) to scan the surfaces of molecules. They have found a method to isolate the target molecule, a single protein, to avoid the effects of protein-to-protein interactions and to make the scanning process faster and more precise.
The new single-molecule HS-AFM approach was used to study a protein called GltPh, which is a transporter located in the cell membrane. This transporter is responsible for directing neurotransmitter molecules into the cell. Structural biologists are particularly interested in studying these transporters due to their complex dynamics and their importance in human health.The researchers were able to gather detailed, real-time data on the structure of GltPh with unprecedented accuracy and stability. This allowed them to observe small fluctuations in the protein’s structure over an extended period of time. They discovered a new state of GltPh in which the transporter is inactive, shedding light on the “wanderlust” phenomenon where the protein switches between high and low activity states without a clear reason.The scientists highlighted that their new method, which they are continuously working to improve, can be applied to the study of various proteins, including those embedded in membranes. In general, they stated that this research opens up new opportunities to monitor the specific structure of a protein moment by moment as it goes through its cycles of activity and rest. This study was funded by the National Institute of Health (NIH), National Center for Complementary and Integrative Health, grant DP1AT010874, and the National Institute of Neurological Disorders and Stroke, R01NS110790.
