Heating Proteins to Body Temperature Uncovers New Drug Targets

Traditionally, proteins are studied at low temperatures to maintain stability. Yet, a recent study illustrates that specific proteins exhibit high sensitivity to temperature and undergo structural changes when observed at body temperature. So heating proteins to body temperature uncovers new drug targets these findings, published today in Nature.

DateMay 15, 2024
SourceVan Andel Research Institute
SummaryA novel method for studying proteins at body temperature reveals that some proteins significantly change their structures when heated, creating new opportunities for structure-guided drug development. The study focused on a protein called TRPM4.
Biology News: Heating proteins to body temperature uncovers new drug targets

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About TRPM4 Protein:

  • Certain proteins alter their shape when exposed to different temperatures and reveal previously unknown binding sites for medications. These findings could transform various areas of biology by fundamentally changing the study of protein structures and their use in drug design.
  • The research centered on TRPM4, a protein essential for heart function and metabolism, including insulin release. Consequently, TRPM4 is associated with various health conditions such as stroke, heart disease, and diabetes.
  • TRPM4 is a type of protein known as a transient receptor potential (TRP) channel. It plays a crucial role in various physiological processes within the body.
  • The TRPM4 protein is a transmembrane protein, meaning it spans the cell membrane. It consists of multiple domains, including transmembrane domains that form the channel pore and regulatory domains that control its activity.
  • The TRPM4 protein is involved in regulating the flow of ions, particularly calcium ions, across cell membranes. It helps control cell signaling, which is essential for numerous functions, including heart function, metabolism, and insulin release.

How Drugs Enter into the Cell Membrane Watch Here

Experiment of How Heating Proteins to Body Temperature Uncovers New Drug Targets:

ExperimentObservationConclusion

To detect TRPM4 at body temperature, the team utilized VAI’s advanced cryo-electron microscopes (cryo-EM). These instruments enable scientists to flash-freeze proteins and create detailed images of their structures, instead of using a low-temperature sample.
This approach revealed that ligands—molecules that bind to proteins—interact with entirely different sites on TRPM4 at body temperature compared to lower temperatures.The findings of this study have extensive implications and underscore the significance of examining proteins at body temperature to accurately identify physiologically relevant drug binding sites.
Biology News: Heating proteins to body temperature uncovers new drug targets

Proteins serve as the molecular engines of the body, with their shape dictating their interactions with other molecules to carry out their functions. By unraveling protein structures, scientists can craft templates that steer the development of more potent medications and thus heating proteins to body temperature uncovers new drug targets.

FAQ:

1. What does it mean to heat proteins to body temperature?

Heating proteins to body temperature refers to subjecting proteins to the same temperature as the human body, approximately 37 degrees Celsius (98.6 degrees Fahrenheit).

2. Why is heating proteins to body temperature important?

Heating proteins to body temperature reveals how they behave under conditions similar to those inside the human body. This can provide insights into their structure and function, including how they interact with potential medications.

3. What are drug targets?

Drug targets are specific molecules, such as proteins, that medications interact with to produce a therapeutic effect. Identifying new drug targets is crucial for developing effective treatments for various diseases.