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Bitter taste is undeniable, but what chemical process causes it? Thanks to new research, we now understand how taste receptors (taste buds) on our tongues are activated at a molecular level. , a breakthrough in taste science.
The research, led by a team at the University of North Carolina (UNC) School of Medicine, links the bitter taste receptor, called TAS2R14, to identifying one of the five different tastes we can detect: sweet, sour, salty, and savory. It focuses on the role of its receptors in helping. Bitter, umami (or flavor).
This builds on what we know about taste and could lead to improved treatments for health conditions linked to the TAS2R14 receptor, including obesity, diabetes, asthma, and chronic obstructive pulmonary disease. There is sex.
“Scientists know very little about the structural makeup of sweet, bitter, and umami taste receptors,” says Yoojoong Kim, a pharmacologist at the UNC School of Medicine.
“By combining biochemical and computational methods, we discovered the structure of the bitter taste receptor TAS2R14 and the mechanism that initializes bitter taste sensation on the tongue.”
These methods include cryo-electron microscopy, which enables ultra-high precision imaging of the 3D structural biology of molecules in their active state by rapidly storing them at ultra-low temperatures. Masu. Scientists can study the function of molecules such as proteins and viruses, which can lead to more targeted treatments for conditions involving those molecules.
The research team revealed that when a bitter substance (or tastant) hits TAS2R14, it bites into the allosteric site. This regulatory region allows the molecule to bind to a protein and influence its functional activity.
This mechanism had not been discovered before. Binding of the tastant to the allosteric site changes the shape of the receptor, activating the bound G protein and triggering a subsequent signaling chain reaction.
In this way, the message is sent to a part of the brain called the taste cortex, where we process the signal and perceive it as bitter.
Another new finding is the involvement of cholesterol, which binds to the active site of TAS2R14 and helps trigger the bitter taste detection process. Bile acids have a similar structure to cholesterol and have previously been associated with TAS2R14 activation.
“Cholesterol was present in a separate binding site called the orthosteric pocket of TAS2R14, while bitter substances were bound to the allosteric site,” Kim says.
“Through molecular dynamics simulations, we also found that cholesterol puts the receptor in a semi-active state, which can be easily activated by bitter substances.”
As for how new discoveries will be used, beyond a deeper understanding of the body’s most complex processes, it may look like a leap from tasting bitters to the health issues mentioned earlier. I don’t know.
But these receptors are also present in the airways and play a role in regulating appetite, and cholesterol and bile acids help control metabolism, so what scientists learned here could help treat related problems. may benefit.
“In the future, this structure will be key to the discovery and design of drug candidates that can directly modulate G proteins through allosteric sites,” says Professor Kim.
This study Nature.
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