According to statistics, more than half of adults in China are currently suffering from overweight or obesity, and about 130 million people suffer from diabetes
In a study published in Nature-Communications on August 20, Jiang Yi, Xu Huaqiang and Xie Xin, researchers from the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, reported for the first time that ghrelin receptors bind to endogenous polypeptide hormones— —The near-atomic resolution structure of ghrelin and growth hormone releasing peptide-6 (GHRP-6), as well as the Gq protein signal complex, reveals the molecular mechanism of ghrelin receptor unique ligand recognition and activation
Food intake is one of the most basic activities to maintain human life.
Important ghrelin
Important ghrelin Ghrelin is currently the only known appetite-stimulating hormone secreted by gastric tissue.
Because of the important physiological functions of the ghrelin system, ghrelin receptors have also become one of the current popular targets for the treatment of metabolic diseases such as obesity and diabetes
Jiang Yi told the Chinese Journal of Science that the stability of the ghrelin receptor complex is poor and it is difficult to obtain a stable sample of the complex.
Lifting the "veil" of the structure
Lifting the "veil" of the structure In order to obtain high-purity and stable complex samples, the research team introduced NanoBiT live cell protein interaction detection technology to stabilize the complex, optimized the purification method of the complex, modified the downstream Gq protein, and analyzed it by cryo-electron microscopy.
In combination with ligand binding and cell function analysis, the researchers revealed the precise binding mode of ghrelin and GHRP-6 with the ghrelin receptor binding pocket, and confirmed that the hydrophobic network composed of receptor residues I178, L181, and F286 is starving.
In addition, the researchers also clarified the key role of the conserved salt bridge between receptor residues E124 and R283 in stabilizing the receptor, explaining the new mechanism by which the activating peptide induces R283 to swing to the receptor helix core, thereby activating the ghrelin receptor
"Next, we will continue to in-depth exploration of the regulation mechanism of ghrelin receptor activity, and carry out drug discovery targeting ghrelin receptor
Related paper information: https://doi.
https://doi.
org/10.
1038/s41467-021-25364-2
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