A recent study published in Nature has uncovered the discovery that certain proteins undergo significant structural changes when exposed to body temperature, revealing previously unknown binding sites for medications. Led by Juan Du, Ph.D., and Wei Lü, Ph.D. at the Van Andel Institute, this groundbreaking research could have a major impact on the field of biology, fundamentally changing how protein structure is studied and utilized in drug design. Traditionally, proteins have been studied at low temperatures to maintain stability, but this new study demonstrates that some proteins are highly sensitive to temperature and exhibit different shapes at body temperature.
Proteins play a crucial role in the body, acting as molecular workhorses that interact with other molecules to perform various functions. Understanding the structure of proteins is essential for developing more effective medications, as it enables scientists to create blueprints that guide drug design. By revealing how proteins change shape at different temperatures, researchers can potentially uncover new opportunities for structure-guided drug development. This shift in perspective could lead to significant advancements in the design of medications, akin to locksmiths designing keys to fit specific locks.
While it is widely known that temperature can impact molecular function in the body, studying proteins at physiological temperatures has posed technological challenges in the past. The Du and Lü laboratories have succeeded in overcoming these obstacles, offering a roadmap for other scientists to study proteins at body temperature in their own experiments. The focus of their study was on a protein called TRPM4, which plays a critical role in supporting heart function, metabolism, and insulin release. This protein is associated with various health conditions such as stroke, heart disease, and diabetes.
To visualize TRPM4 at body temperature, the researchers used cryo-electron microscopes at the Van Andel Institute, which allow for detailed imaging of protein structures by flash freezing them. By heating the sample to body temperature before freezing, they discovered that the ligands interacting with TRPM4 bind to different sites at body temperature than at lower temperatures. This finding highlights the importance of studying proteins at physiological temperatures to identify relevant drug binding sites, as it may lead to more targeted and effective drug designs that can address various health conditions more efficiently.
The implications of this study are far-reaching, emphasizing the significance of studying proteins at body temperature to gain a deeper understanding of their structures and functions. By uncovering new binding sites for medications and understanding how proteins change shape in response to temperature, researchers can revolutionize drug design and development. This research sheds light on the molecular mechanisms underlying protein function and highlights the potential for future advancements in the field of biology and medicine. Scientists can leverage this newfound knowledge to advance drug discovery and improve treatments for a wide range of health conditions.