Molecule of the Month: Monellin

Sugar tastes sweet for a good reason: it’s a fast and easy source of energy for our cells, so evolution has ensured that we’re happy when we eat it. Cells in our taste buds have specific sensors for sugar, rewarding us with a pleasant taste for sugary foods. However, other molecules can trick these sensors, giving us the reward but without the calories. These include small artificial molecules that resemble sugar, such as aspartame, and a variety of sweet-tasting proteins.

Several intensely sweet proteins have been discovered in African plants, including monellin (PDB entry 3mon), thaumatin (PDB entry 1thv), and brazzein (PDB entry 2brz). Molecule-for-molecule, these small proteins are 100,000 times sweeter than sugar, so we only need tiny amounts of them to get the same sweet taste. When these proteins were first discovered, researchers hypothesized that they would have a little extension that would mimic a sugar molecule. When structures were solved, however, these were not seen, and the current theory sees them acting as a wedge to lock sweet receptors in their active conformation.

Several other proteins discovered in tropical plants have an even more unusual property: they can change the taste of foods. Neoculin (PDB entry 2d04) and miraculin (not shown) can change sour foods into sweet foods. They have amino acids that change properties in acidic (sour) environments, and then stimulate our sweet receptors, making us think we’ve eaten something sweet. Gurmarin (PDB entry 1c4e) has just the opposite property—it is a taste suppressor that blocks the sensing of sugar, so sweet foods don’t taste sweet at all.

Our sense of sweet taste is managed by a single type of receptor, called TIR2/TIR3, which is similar in structure to the glutamate receptor shown here (PDB entries 2e4z and 4or2). It is composed of two parts: a domain on the outside of the cell that binds to sugar and a typical GPCR domain that crosses the cell membrane, delivering the signal inside. Monellin and other sweet-tasting proteins are thought to bind in the large cleft that surrounds the small sugar binding site, tricking the receptor into thinking that sugar has bound.