Some proteins have been discovered to change their shape when they are exposed to different temperatures. This change in shape has revealed previously unknown binding sites for medications. These new findings have the potential to greatly impact the field of biology, as they fundamentally change how protein structure is studied and used in the design of drugs. The study was published today in Nature.The study, led by Juan Du, Ph.D., and Wei Lü, Ph.D. of Van Andel Institute, focused on protein design. Typically, proteins are examined at low temperatures to maintain their stability. However, the study found that certain proteins are very sensitive to temperature and will change shape when observed at body temperature.
According to Du, “For a long time, the methods we’ve used to study proteins require them to be cold or frozen. But in the real world, human proteins exist and function at body temperature.” The study introduces a new approach to studying proteins at body temperature and uncovers that some proteins undergo significant structural changes.
At higher temperatures, proteins undergo structural changes that can be advantageous for developing drugs.
Proteins play a vital role in the body and their shape determines their functionality when interacting with other molecules. Understanding their structure allows scientists to design more effective medications, similar to how locksmiths create keys for specific locks.
While it is common knowledge that temperature impacts molecular function, studying proteins at physiological temperature has been difficult. The recent study by the Du and Lü laboratories explains how they overcame these challenges.The article discusses issues related to studying the protein TRPM4 and presents a guide for scientists to conduct their own experiments. The focus of the study was on the function of TRPM4 in supporting heart function, metabolism, and insulin release, with implications for stroke, heart disease, and diabetes. The team utilized VAI’s cryo-electron microscopes to visualize TRPM4 at body temperature, enabling them to generate detailed images of the protein’s structure by flash freezing it. Instead of using a low-temperature sample, the researchers leveraged the advanced technology to study TRPM4.The research laboratories raised the temperature of the sample to match that of the human body before suddenly freezing it. This method revealed that molecules known as ligands, which attach to proteins, interact with different areas on TRPM4 at body temperature compared to lower temperatures.
This study’s findings have wide-ranging implications and emphasize the importance of examining proteins at body temperature to accurately identify drug binding sites that are relevant to the body’s physiology.
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