A hidden pocket in the bitter taste receptor has been discovered in the human body

The research shows that the TAS2R receptors are involved in many processes such as breathing, digestion and the immune system. "The opposite sense of taste: an unusual sensory mechanism discovered in the detection of bitter taste in humans"

New research reveals that certain molecules that trigger a bitter sensation bind to their taste receptor at two different points at the same time: one outside the cell and the other inside it. This finding is fascinating because the bitter taste receptors are expressed in tissues that are not directly related to the sense of taste, and shows the ability of our cells to sense not only external but also internal stimuli. The discovery opens up new possibilities for drug design, including for the treatment of asthma and inflammation.

The research, published in the journal Nature Communications, was led by Prof. Masha Niv from the Hebrew University of Jerusalem, Dr. Moran Shalb-Banami from the Weizmann Institute, and Dr. Dorothy Weickert from the University of Erlangen, Germany. The study described a fascinating discovery of a hidden "pocket" inside one of the body's bitter taste receptors, TAS2R14. This breakthrough not only explains how our tongue senses bitterness, but also reveals the physiological roles of the bitter taste receptors that appear in other organs.

The science behind the discovery

In the human body there are 25 different receptors to identify diverse chemical molecules that evoke a feeling of bitterness. The TAS2R14 receptor turns out to be unique, thanks to its ability to bind a wide variety of substances, from vitamins to drugs and odors. Until now, it was not clear how he manages to bind these substances and cause a physiological response.

Using advanced electron microscopy (cryo-EM) technology, the scientists were able to identify the three-dimensional structure of the TAS2R14 receptor along with an anti-inflammatory drug called flupenamic acid (FFA), which stimulates the receptor. It turned out that the drug binds simultaneously in two separate locations: one outside the cell and the other inside the cell. This finding offers new insights into how the receptor works in contact with various chemical substances.

medical implications

"This is a discovery that changes the rules of the game," says Prof. Niv. "The receptor not only recognizes chemicals outside the cell, such as food or drugs, but also 'tastes' internal processes within the cell itself. The newly discovered inner pocket can be used by us in the design of new drugs."

In addition, Dr. Dorothy Weickert adds: "We developed an innovative method for measuring the connectivity of molecules specifically at the extracellular and intracellular binding sites, which opens doors to unique scientific discoveries."

The research shows that the TAS2R receptors are involved in many processes such as breathing, digestion and the immune system. "By discovering the new pocket, we have opened up new possibilities for designing drugs to treat conditions such as asthma, obesity and inflammation," added researchers Lior Perry and Dr. Matsov.

for the scientific article