Scientists from Leipzig University and the Charité Clinic in Berlin have discovered the protein MRAP2, which regulates the work of the appetite receptor MC4R and helps to “turn off” the feeling of hunger. The study, published in Nature Communications, reveals a new mechanism for controlling satiety and could form the basis for developing effective methods to combat obesity and metabolic disorders.
A group of researchers from Leipzig University and Charité – Universitätsmedizin Berlin made an important discovery in the field of neurobiology and metabolism. The scientists identified the protein MRAP2 (Melanocortin-2 Receptor Accessory Protein 2), which regulates the transport of the appetite receptor MC4R to the cell surface. This receptor is precisely what is responsible for transmitting satiety signals and ending the feeling of hunger.
“We are proud to demonstrate that our Center contributed to the understanding of receptor transport,” noted Professor Annette Beck-Sickinger.
The MC4R receptor is activated by the hormone MSH and is considered one of the key targets in obesity therapy. Mutations in its structure are one of the most common causes of severe human obesity. Using fluorescence microscopy methods, the scientists proved that without MRAP2, the receptors remain inside the cell and are unable to perform their function.
“This discovery has therapeutic potential in the fight against metabolic diseases,” emphasized Professor Heike Bieberstein.
Researchers had previously deciphered the three-dimensional structure of active MC4R, which allowed for a deeper understanding of its mechanism of action and helped explain how modern drugs—such as setmelanotide—reduce appetite.
The work was published in the journal Nature Communications and was carried out as part of the four-year CRC 1423 project, which unites scientists from five German universities. The project is funded by the DFG and aims to study the structural dynamics of GPCR receptors, key regulators of many physiological processes.
